|Year : 2012 | Volume
| Issue : 3 | Page : 160-200
ICRT-Abstracts of Poster Presentations
|Date of Web Publication||10-Nov-2012|
|How to cite this article:|
. ICRT-Abstracts of Poster Presentations. World J Nucl Med 2012;11:160-200
What is the Alternative to Radioiodine Therapy in Diffuse Pulmonary Metastasis from Papillary Thyroid Carcinoma in Children
C. Kaouthar, K. Tarek, N. Manel, S. Raja, B. Maha, A. Najla, G. Mohsen, E. Habib
Department of Nuclear Medicine, Sahloul University Hospital, Sousse, Tunisia
Aim: The aim of this study was to report three cases of children who had papillary thyroid carcinoma with diffuse pulmonary metastases treated by radioiodine. Radioiodine cumulative activity and follow-up were discussed.
Materials and Methods: We reviewed retrospectively the data of patients with diffuse pulmonary metastasis from papillary thyroid carcinoma. Patients with a follow-up of over 4 years were reviewed.
Results: The three patients (two females/one male) were aged, respectively, 13, 14, and 8 years, when they were operated. Papillary thyroid carcinoma was classified pT3pN1bM1 in one case and pT4pN1bM1 in two. All of them had high initial Tg and an initial diffuse pulmonary uptake of radioiodine clearly visible behind the remnant thyroid uptake. Radioiodine therapy was stopped in two patients who had had a cumulative activity of 74 and 51 GBq, respectively. Hemogram and spirometry were always normal. The latest scans showed fairly diffuse pulmonary uptake and Tg was decreased (16 and 42 ng/ml, respectively). A third patient (8 years) had an activity of 25 GBq. The latest scan (March 2012) showed the persistence of diffuse pulmonary uptake; Tg was high (167 ng/ml, normal < 0.1). Unfortunately, the spirometry control showed a partial restrictive syndrome. Continuation of radioiodine therapy was then discussed.
Conclusion: Radioiodine is the treatment for pulmonary diffuse metastases from papillary thyroid carcinoma. Stabilization of the disease can be achieved after a high cumulative activity. But when a restrictive pulmonary syndrome appeared in a child of 12 years, radioiodine therapy is discussed, but what is the alternative to radioiodine therapy in diffuse pulmonary metastases from papillary thyroid carcinoma in children?
Thyroid Cancer Treated at the Clinical Center Banja Luka: A 5-year Experience
Z. Rajkovaca, J. Brstilo, S. Bobic
Department of Nuclear Medicine, Clinical Center, Banja Luka, Bosnia and Herzegovina
We performed a retrospective study of 297 patients (63 males and 234 females) with pathological proven thyroid cancer who had received radioiodine treatment at our hospital during the period August 2006-August 2011. The follow-up period was between 5.5 years and 5 months, an average of 38 months. The median age of the cohort at radioiodine ablation was 51.3 (range 14-82) years, with a little difference between the sexes (49.9 years for males and 58.7 years for females). Female: male ratio was 3.7:1. A total of 68 (29%) women and 15 (23.8%) men were younger than 45 years. In all patients, these were performed-subtotal or total thyroidectomy and radioiodine treatment of remnant of thyroid gland. Thyroid function tests including thyroid stimulating hormone (TSH), free thyroxin (FT4), thyroglobulin (tg), and anti-thyroglobulin antibody (tg-ab) were performed on the day of radioiodine treatment. Among these patients, there were 229 cases of papillary, 58 cases of follicular, and 10 cases of Hurtle cell cancer. Papillary: follicular ratio was 3.9:1. In 175 (58.9%) patients there was no cancer spread outside the thyroid gland; it was N0M0 stage. One hundred and sixty-two (92.5%) patients received a single dose range between 1480 and 3700 MBq. Thirteen (7.5%) patients received a second dose of activity 3700 MBq. None of these patients died during the follow-up period. One hundred and two (34.4%) patients had metastatic lymph nodes and it was N1M0 stage; 94 (92.1%) received a single dose range between 2960 and 3700 MBq. Eight (7.9%) received a second dose of activity 3700 MBq. None of these patients died during the follow-up period. Twenty (6.7%) patients had distant metastatic lesions, 11 in lungs and 9 in bones. All of them received minimum two doses of activity 2950 MBq. Five of these patients died during the follow-up period. All five patients had papillary carcinoma.
Optimization of 90Y-antiCD20 Preparation for Radioimmunotherapy
A. R. Jalilian
Medical Physics, Tehran University of Medical Sciences, Tehran, Iran
The optimization of 90Y-antiCD20 radioimmunoconjugate production and quality control methods for future clinical studies in the country was targeted in this work. The antibody was labeled with 90Y-yttrium chloride (185 MBq) after conjugation with freshly prepared ccDTPA. Y-90 chloride was obtained by thermal neutron flux (4 × 1013 n/cm 2 /s) of a natural Y2O3 sample dissolved in acidic media. Radiolabeling was completed in 24 h by the addition of DTPA-rituximab conjugate at room temperature. Radiochemical purity of 96% (using ITLC) was obtained for final radioimmunoconjugate (specific activity = 440-480 MBq/mg). The final isotonic 90Y-rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were carried out and performed to determine the radioimmunoconjugate distribution up to 72 h.
Optimized Preparation of [64Cu]-DOTA-trastuzumab for PET Applications
A. R. Jalilian
Medical Physics, Tehran University of Medical Sciences, Tehran, Iran
Objective: Breast cancer radioimmunoscintigraphy targeting HER2/neu expression is a growing field of work in nuclear medicine research. Trastuzumab is a monoclonal antibody that binds with high affinity to HER2/neu, which is overexpressed on breast and other tumors. Developing new tracers for the detection of this cancer is of great interest.
Materials and Methods: In this study, trastuzumab was successively labeled with [64Cu] CuCl2 after conjugation with DOTA-NHS-ester. The conjugates were purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated, and total concentration was determined by spectrophotometric method. DOTA-trastuzumab was labeled with 64Cu produced by 68Zn (p, an) 64Cu nuclear reaction (30 MeV protons at 180 mA). Radiochemical purity, integrity of protein after radiolabeling, and immunoreactivity of radiolabeled mAb trastuzumab with HER2/neu antigen and SkBr3 cell line were determined by radioimmunoassay (RIA). In vitro stability of radiolabeled mAb in human serum was determined by thin layer chromatography (TLC). In vitro internalization studies were performed with the SkBr3 cell line and the tissue biodistribution of the 64Cu-DOTA-trastuzumab was evaluated in wild-type rat (60 ± 5.5 mCi, 2 h, 6 h, 12 h, 24 h p.i.).
Results: The radioimmunoconjugate was prepared with a radiochemical purity of higher than 96 ± 0.5% (RTLC). The average number of chelators per antibody (c/a) for the conjugate used in this study was 5.8/1. The sample showed to have similar patterns of migration in the gel electrophoresis. The 64Cu-DOTA-trastuzumab showed high immunoreactivity toward HER2/neu antigen and SkBr3 cell line. In vitro stability of the labeled product was found to be more than 94% in Phosphate buffered saline (PBS) and 82 ± 0.5% in human serum over 48 h. In vitro internalization studies of the 64Cu-DOTA-trastuzumab showed that up to 12% of the radioimmunoconjugate internalized after 10 h. The accumulation of the radiolabeled mAb in liver, skin, intestine, lung, spleen, kidney, and other tissues demonstrates a similar pattern to the other radiolabeled anti-HER2 immunoconjugates.
Conclusion: 64Cu-DOTA-trastuzumab is a potential compound for molecular imaging of positron emission tomography (PET) for diagnosis and treatment studies and follow-up of HER2 expression in oncology.
Significance of Post-therapy SPECT-CT Scans in Differentiated Thyroid Cancer
R. Kumar, Vasumathi, S. Oommen
Department of Nuclear Medicine, Kasturba Medical College, Manipal University, Manipal, India
Objective: This case report aims to highlight the importance of post-therapy SPECT-CT scan in differentiated thyroid cancer patients.
Materials and Methods: A 58-year-old female underwent total thyroidectomy for thyroid nodule. Histopathology revealed widely invasive follicular carcinoma thyroid. I-131 whole body scan subsequently done after proper preparation showed residual thyroid tissue only and was treated with 105 mCi I-131 on the same day. Post-therapy whole body scan done 48 h later showed residual thyroid tissue only. She was started on suppressive dose of thyroxin. Eight months later, an I-131 whole body scan was performed after adequate preparation. The scan did not show any e/o residual thyroid tissue, but a focal uptake was seen in the right lower thoracic region, which was more prominent in posterior view. A planar chest radiograph showed a small round opacity measuring 2.0 2.0 cm along the 11 th rib in the mid-clavicular line in the right hypochondrial region, possibly a calcified granuloma in the liver. An ultrasound of abdomen subsequently done did not reveal any abnormality in the liver or any other abdominal organ. Planned for another radioiodine therapy; and a dose of 157 mCi I-131 was administered orally. Seventy-two hours later, a post-therapy whole body scan was performed. The post-therapy planar scan showed a focal uptake in both lower thoracic regions. At this point, a SPECT-CT of the thoracic region was done. SPECT-CT revealed two focal uptakes in lower zone of right lung and one focal uptake in lower zone of left lung.
Results: The post-therapy planar scan showed a focal uptake in left lower thoracic region, which was not seen in the pre-therapy planar scan. This lesion was confirmed by SPECT-CT to be a left lower lung metastasis. The focal uptake which was seen in the right lower thoracic region in the pre-therapy planar scan and suspected to be a calcified granuloma in the liver on radiograph was actually detected on SPECT-CT to be a focal metastasis in lower zone of right lung situated posteriorly. Additionally, SPECT-CT displayed a new focal uptake in the lower zone of right lung, which was found to be located just superior to the previous lesion.
Conclusion: Post-therapy scans have higher sensitivity compared to the pre-therapy scans. SPECT-CT helps in better characterization of the lesions and has an incremental diagnostic value over the planar imaging.
Patient's Specific Dosimetry for Radioiodine Therapy of Thyroid Cancer and Comparison with Fixed Doses
N. Marwat, M. T. Hussain Khan, S. Fatima, S. Farruq, R. Hussain
Medical Physics, Nuclear Medicine Oncology and Radiotherapy Institute, Islamabad, Pakistan
Radioiodine therapy is one of the treatments for thyroid cancer and is widely accepted. It is considered to be safe, relatively inexpensive, and convenient for patient, and also has very small number of side effects. Radioiodine therapy is common, but approach of treatment is different in different countries. There are two common approaches, fixed-dose method and dosimetry. In almost all PAEC hospitals, fixed-dose method is considered to be the method of choice by a majority of nuclear physicians. In this method, the nuclear physician gives activity to the patient with thyroid cancer, based on their personal clinical judgment. It is given without considering physiological behavior of I-131 in individual patients. Effective decay varies from patient to patient. So, in this method, there are greater chances of overdosing and underdosing. This research was conducted in Nuclear, Oncology and Radiotherapy Institute (NORI) during March-June 2011. In this institute, high-dose method was being followed in which there were greater chances of overdoses to the patients. Blood dosimetry with single measurement was performed to calculate the blood dose, which is considered to be 14% of total body dose contribution to the bone marrow dose. Ten patients were selected for this study. Overdoses to bone marrow were seen in the patients frequently. Overdose to bone marrow is alarming as it is one of the critical organs. A simple formula for blood dosimetry with single measurement for bone marrow was used in 6 out of 10 patients who received overdoses to bone marrow, which is alarming. This research stresses on the need of internal dosimetry in all other hospitals where radioiodine therapy is being performed by fixed-dose method.
Bone Metastases from Differentiated Thyroid Carcinoma: Clinical Features and Long-term Follow-up
N. Nahar, Sultana Sadia, M. Mokaddema
Department of Nuclear Medicine, Institute of Nuclear Medicine and Ultrasound, Dhaka, Bangladesh
Bone is the second most frequent site of metastasis resulting from thyroid cancer. The purpose of this study was to review clinical characteristics of bone metastasis originating from thyroid cancer and their response to treatment. From 1980 to 2009, bone metastases were found in 67 out of 1804 differentiated thyroid carcinoma patients sent for radioiodine treatment in our institute. Bone metastasis was the presenting symptom in 48 (71.5%) patients, detected from the clinical investigation in 14 (20.5%) patients, and occurred subsequently in 5 (7.5%) patients. Pathological pattern of the thyroid cancer was follicular in 49 (73%) patients, follicular variant of papillary in 10 (15%) patients, and papillary in 8 (12%) patients. Bone metastatic involvement was solitary in 32 (48%), multiple in 35 (52%) patients, and associated with other synchronous or metachronous distant metastases in 25 (37%) patients, especially in the lung. In all 67 patients, areas of bone metastases concentrated 131 I. MDP bone scan was done in 40 patients and 39 (97.5%) of them showed positive bone scan. Fifty-six patients underwent local X-ray and 53 (94.6 %) of them showed positive radiological findings. In our institute, thyroglobulin (Tg) estimation is done regularly from 1998. Baseline Tg was done in 39 patients and 33 (84.6%) of them showed high value. The primary treatment of thyroid carcinoma was total thyroidectomy in all 67 patients, with additional modified neck dissection in 9 patients and excision of bone mass in 26 patients. All 67 patients with functioning bone metastases were given 131 I therapy. In addition, 29 patients got radiotherapy and 2 patients got chemotherapy. Treatment response was evaluated by whole body large dose scan and serum Tg measurement. Complete response to therapy of bone metastases was defined as the absence of clinical symptoms, negative 131 I whole body scan, and low or undetectable Tg. Seven patients were lost to follow-up. Among the rest 60 patients, a 5-year follow-up showed disease-free condition in 14 (23%) patients. Thirteen (22%) patients improved, and in 8 patients (14%), the condition remained almost unchanged. In 20 (33%) patients, the condition worsened with progression of disease and 5 (8%) patients died. Metastatic thyroid cancer (bone metastases), when treated properly and in time, can be cured in a number of cases. In other cases, palliation can be achieved and survival time can be enhanced with an improved quality of life. With 131 I therapy, other available treatment options like surgery, radio or chemotherapy should be considered.
Salivary Gland Tumor after Radioiodine Therapy for Well-Differentiated Thyroid Carcinoma: A Case Report
L. Nisa, S. Yasmeen, F. S. Haq, N. Nahar, S. Sultana, Z. Jabin
Nuclear Medicine, Institute of Nuclear Medicine, Dhaka, Bangladesh
A case of poorly differentiated salivary muco-epidermoid cancer, which developed after radioiodine therapy for papillary thyroid carcinoma with metastases, is reported. Though this case represents only 7.2% of all the cases treated at the Institute of Nuclear Medicine, Dhaka, it nevertheless stresses the importance of consistently protecting the salivary gland during radioiodine therapy to reduce radiation injury. Also, long-term follow-up of patients treated with radioiodine is emphasized in order to detect secondary malignancies at the earliest.
Radioactive Iodine Ablation in Children and Adolescents with Differentiated Thyroid Carcinoma
Y. T. Jelani, B. Hidayat, B. Darmawan, A. H. S. Kartamihardja, J. S. Masjur
Department of Nuclear Medicine, Universitas Padjadjaran, Bandung, Indonesia
Background: The prevalence of thyroid carcinoma in children and adolescents is about 10% of thyroid malignancy cases. We reported our experience in using radioactive iodine (NaI-131) ablation for children and adolescents with post-total thyroidectomy differentiated thyroid carcinoma.
Materials and Methods: A retrospective study was conducted in children and adolescent subjects with differentiated thyroid carcinoma who had undergone post-total thyroidectomy followed by radioiodine ablation therapy. Data were collected from 25 medical records in our department from 1998 to 2010. Histological and laboratory findings [serum TSHs, thyroglobulin (Tg), and anti-thyroglobulin antibody (ATA) levels] were noted until at least 6 months after ablation. Only 15 patients were eligible. Complete response after ablation was defined if Tg serum level was <3 ng/ml, with TSHs serum level >30 mIU/ml and no detected ATA level; outside this level was defined as residual disease.
Results: Of 15 subjects (12 females and 3 males, aged 13-21 years), 9 subjects were papillary thyroid carcinoma (PTC) (60%) and 6 subjects were follicular thyroid carcinoma (FTC) (40%). Metastases were found in 5 subjects (33.3%) with loco-regional lymphatic metastases, 3 subjects (20%) with pulmonary metastases, 1 subject (6.6%) with bone metastases, and 1 subject (6.6%) with metastases in soft tissue. The first ablation I-131 dose given was between 80 and 100 mCi. Next I-131 was given after 6-12 months or more, if needed, by increasing the dose to 150 mCi. Three subjects (1 PTC, 2 FTC) had complete response after first ablation, one subject (PTC) after the second dose, and one subject (PTC) after the third dose. Four of five subjects had Tg serum level <10 ng/dl. Eighteen months after radioiodine ablation, 10 subjects (66.6%) were categorized as residual cases with Tg serum levels of more than 10 ng/dl.
Conclusion: The mainstream management of differentiated thyroid carcinoma is total thyroidectomy, followed by radioactive iodine (I-131) ablation and suppressive doses of thyroid hormone. Complete response was found in three subjects after 6 months of radioactive iodine ablation. Other studies used Tg serum level <3 ng/dl as the criterion of good response to therapy. Based on these criteria, good response was found in four patients with Tg serum level <3 ng/dl. PTC in children has a favorable prognosis. The favorable prognosis is associated with lymphocytic infiltration, as an anticancer reaction during the immunologic activity. Children usually have more advanced tumors, with local and distant metastases and higher recurrence rates. Children under 10 years of age have very high mortality rates. In conclusion, it seems that age, histopathology classification, and distant nodal metastases are the important factors for non-responsiveness of well-differentiated thyroid carcinoma in children and adolescents to radiothyroablation therapy.
The Advantages of Routine Radiothyroablation in Well-Differentiated Thyroid Carcinoma Patients
H. Indrawati, B. Hidayat, B. Darmawan, A. H. S. Kartamihardja
Department of Nuclear Medicine, Medical Faculty of Padjajaran University, Bandung, Indonesia
Background: Routine radiothyroablation following total thyroidectomy remains controversial in well-differentiated thyroid cancer. Thyroid remnant is commonly found even after total thyroidectomy. In our institution (Dr. Hasan Sadikin Hospital), we use routine Radioactive iodine (RAI) therapy for thyroid remnant ablation and unsuspected metastases that were subsequently seen from post-therapy whole body scans. The purpose of this study was to evaluate the advantages of routine ablation in differentiated thyroid carcinoma (DTC) patients.
Materials and Methods: The retrospective study was conducted on patients diagnosed with DTC and subsequently treated with routine ablation therapy after total thyroidectomy from January 2009 to December 2010. Routine ablation was given 6-8 weeks after total thyroidectomy. I-131 therapeutic dose was varied between 80 and 200 mCi (2960-7400 MBq). WBS and SPECT/CT post-therapy were performed when patients were discharged to evaluate pathological extrathyroidal uptake of I-131.
Results: A total of 133 patients (103 females and 30 males; 13-72 years old) were included in this study. Papillary carcinoma was diagnosed in 95 patients and the rest had follicular carcinoma. There were pathological extrathyroidal uptakes of I-131 in 33 cases. Twenty-six of them were unsuspected with pathological extrathyroidal uptakes, while seven others were referred with prior history of distant metastases. Two of the seven cases did not show any pathological uptake of I-131 as predicted before. Imaging was able to show more metastatic lesions in the other five.
Conclusion: I-131 routine ablation exhibits advantages in differentiated thyroid carcinoma patients as it is able to detect unsuspected distant metastases and provide guidance for more suitable management.
Clinical Outcome of Differentiated Thyroid Carcinoma with Lymph Node Metastasis: A Retrospective Analysis at a Single Institute
F. Nasreen, N. Nahar, S. Sultana, Z. Jabin, F. Haque, M. U. Mokaddema, F. Alam
Department of Nuclear Medicine, Institute of Nuclear Medicine and Ultrasound, Dhaka, Bangladesh
Objective: To evaluate the clinical outcome of differentiated thyroid carcinoma (DTC) with lymph node metastases treated with radioiodine ablation at a single institution.
Materials and Methods: A retrospective analysis of 218 patients with DTC and lymph node metastases enrolled in the Institute of Nuclear Medicine and Ultrasound, Dhaka, during the period January 1998-December 2007 was carried out. All patients were treated by thyroidectomy, conservative or aggressive lymphadenectomy, followed by radioactive iodine. Whole body scans, Tg, anti-Tg, and neck ultrasound findings were recorded to classify patients into complete response (CP), partial response (PR), stable disease (SD), and progressive disease (PD) at the endpoint of follow-up.
Results: A total of 193 had papillary carcinoma, 20 had follicular variant of papillary carcinoma, and 5 had follicular carcinoma. There were 83 male patients and 135 female patients. The number of patients <45 years was 159 and those ≥45 numbered 59. Seventy patients had CR, 10% had PR, 7% had SD, and 9% had PD. Nine patients (4%) died among whom five were cause-specific death.
Conclusion: The outcome of DTC patients with lymph node metastases treated with radioactive iodine leads to better survival; regular follow-up reduces the morbidity. Patients who do not respond to radioiodine have worse prognosis.
Papillary Thyroid Carcinoma after Maximum Radioiodine Therapy with Persistent Disease: A Case Study
R. Z. Martiana, B. Hidayat, A. H. S. Kartamihardja
Department of Nuclear Medicine, Faculty of Medicine, Universitas Padjajaran, Bandung, Indonesia
Follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) are well-differentiated thyroid carcinomas, with PTC seen in about 75% of all cases. Recommended therapy for PTC is surgery followed by radiothyroablation using NAI-131 (RAI), and TSH suppression with levothyroxin administration.
Case: A 28-year-old woman, post-total thyroidectomy in 2002, histopathology: Infiltrating PTC into extra-capsular region and lymph node metastasis. She had six radioiodine therapies with a total dose of 830 mCi and never achieved remission.
Staging: Tumor size was 2 cm and it spread to nearby lymph nodes. According to the AJCC TNM system, she had T1N1M0; her age was <45 years. She had stage 1 disease. AGES score for this patient was 0.4 (low risk). AMES classified this patient into high risk because of the extra-capsular tumor tissue. MACIS score was 3.7 (low risk).
Prognosis: Based on the stage and risk criteria, the patient should have had good prognosis. Based on the risk stratification of the American Thyroid Association (ATA), she had an intermediate risk of recurrent disease because of microscopic invasion to peri-thyroid tissue. Thyroglobulin level was found to be 9.1 ng/ml. Whole body scan showed increased radioactivity uptake in retro-sternal and supraclavicular regions. Laboratory and WBS finding showed recurrent disease.
Problem: Young woman with PTC had 830 mCi of radioiodine therapy and showed persistent disease.
Suggestion for this Patient: Ultrasound or anatomic imaging on the area with high radioactivity uptake (retro-sternal and supra-clavicular). Surgery is suggested whenever the lesion is respectable, and subsequently administration of radioiodine with maximal safe dose.
Clinical Behavior of Follicular Variant of Papillary Thyroid Carcinomas at INMU
S. Sultana, N. Nahar, F. H. Haque
Department of Nuclear Medicine, Institute of Nuclear Medicine and Ultrasound, Dhaka, Bangladesh
The clinical behavior of follicular variant of papillary thyroid carcinoma (FVPTC) is the same as that of papillary thyroid carcinomas (PTC). A retrospective study was conducted at the Institute of Nuclear Medicine and Ultrasound (INMU) to analyze the clinical behavior of FVPTC in our population. The medical records of about 2402 patients with thyroid carcinoma treated with radioactive iodine ( 131 I) were analyzed to identify the patients with FVPCT and evaluate the following variables: Age at diagnosis, sex, presence or absence of metastases at the time of diagnosis, and their clinical course after radioiodine ablation. The median follow-up was 6.2 years. The median age was 44 years. Majority of the patients showed no metastases at the time of diagnosis and remained disease free during the period of follow-up. Patients with distant metastases have aggressive outcome. Among these patients, lymph node metastases showed favorable outcome than those with lung and bone metastases. The clinical behavior of FVPTC at INMU is the same as reported in literature.
Detection and Treatment of Lung Metastases in Differentiated Thyroid Carcinoma
Department of Nuclear Medicine and Ultrasound, Institute of Nuclear Medicine and Ultrasound, Dhaka, Bangladesh
Distant metastases at presentation are rare in well-differentiated thyroid cancer (WDTC). This study shows the usual pattern of patients presenting with distant metastases and managed by thyroidectomy and radioactive iodine therapy in our clinical practice, and being offered lifelong follow-up by us, the nuclear medicine and thyroid physicians. We assessed the results of treatment in patients attending Institute of Nuclear Medicine and ultrasound with lung metastases from differentiated thyroid carcinoma, who were followed for up to a decade (minimum of 36 months) after the discovery of the metastases. All were treated with total or near-total thyroidectomy, radioiodine, and L-thyroxin. The prognostic pattern was assessed with interesting points regarding the age at diagnosis, sex, histologic type, tumor extension, associated cervical lymph node metastases, mediastinal metastases, presence of metastases in distant sites other than lungs (multiple distant metastases), and morphological (chest X-rays) and functional (I-131 uptake) features of lung metastases. Most of the patients with lung metastases received multiple ablation doses with radioiodine, which is the most powerful prognostic indicator, but survival rates vary and it appeared that extensive metastases, older age at discovery of the metastases, and absence of radioiodine uptake by the metastatic site are bad prognostic factors. As the overall prognosis is not as poor as many other human cancers, our aim of management is to detect and treat metastases in patients with thyroid cancer as early as possible and maintain their quality of life.
Clinical Significance of Thyroglobulin Antibody Pattern in Patients with Differentiated
I. D. Mulyanto, A. H. S. Kartamihardja
Department of Nuclear Medicine, Dr. Hasan Sadikin Hospital, Bandung, Indonesia
Background: Serum thyroglobulin (Tg) is one of the most important follow-up parameters in patients with differentiated thyroid carcinoma (DTC). The presence of thyroglobulin antibodies (TgAb) may interfere with Tg measurement by resulting in either over- or underestimated serum Tg level. The aim of this retrospective study was to evaluate the role of serum TgAb level pattern in depicting the disease status of DTC patients.
Materials and Methods: Post total thyroidectomy DTC patients who showed positive TgAb after remnant ablation were included. Serum TgAb level was measured in levothyroxine withdrawal. All patients had received minimum three times of radioiodine therapy on average. Residual and remission of disease were qualitatively and semi-quantitatively analyzed from two consecutive post-radioiodine therapies' whole body scans (WBS).
Results: Sixteen DTC patients with positive TgAb were classified into increasing (6 of 16) and decreasing (10 of 16) groups. From increasing TgAb group, four patients showed positive TgAb 6 months post remnant ablation while the other two showed positive TgAb >1 year after remnant ablation. Only one patient of increasing TgAb group showed remission; the rest of patients showed residual disease with higher lesion number or increased radioactive uptake. Patients of decreasing TgAb group showed remission with smaller lesion number or decreased radioactive uptake, except two patients who showed progression despite decreasing TgAb. All patients with discordant results had high serum Tg level.
Conclusion: The pattern of TgAb level may depict disease status in patients with DTC, especially those with low Tg level.
Two Cases with Unusual Uptake in the Whole Body Scan with Radioiodine 131: Textiloma, Miliary Tuberculosis
B. R. Nozha, G. Imad, G. Hasna, M. Ayat
Department of Nuclear Medicine, IBN Sina Hospita Chis IBN Sina, Rabat, Morocco
Despite its good sensitivity and specificity, the whole body scintigraphy with iodine-131 may present many false positives. These artifacts can compromise the correct interpretation of the examination. We will discuss these case reports: Miliary tuberculosis and textiloma. Tuberculosis is common, but the subject is to illustrate another source of false positive with radioiodine, which so far has not yet been reported. It is the case of a patient followed up for operated follicular thyroid carcinoma and who presented a mass simulating a cervical lymphadenopathy. The scan performed 8 days after administration of therapeutic dose of I131 revealed the tracer uptake at this mass. However, after reoperation, we were surprised to be in front of a foreign body, a textiloma. In this paper, we try to discuss the pathophysiological hypotheses that may explain the fixation of I131 at the foreign body.
A Rare Pediatric Case of Metastatic Papillary Thyroid Carcinoma in the Brain
K. Dela Cruz, J. R. Agga, J. Torres
Nuclear Medicine, University of Santo Tomas Hospital, Manila, Philippines
Papillary thyroid carcinoma has a generally indolent course and good prognosis unless it is associated with any distant metastases. Brain metastases from papillary thyroid cancer only occur in less than 1% of the population. It is so rare that preclinical diagnosis is difficult. It is commonly accompanied by hemorrhage, and the prognosis after such a crisis is poor. Early detection of brain metastases is important because of its associated high mortality rates. Prognosis may be improved by surgical resection of brain metastases. It is important that each case be thoroughly assessed and management should be tailored to the needs of each individual patient. The early pre-therapy I-131 whole body scan diagnosis and I-131 therapy of metastases is an important factor in the survival rate and a prolonged disease-free time interval in these patients. Recognizing rare distant metastases has a crucial role in the clinical decision-making and prognosis of patients with thyroid carcinoma.
Diagnostic Difficulty Due To Incidental Fibrous Dysplasia in a Patient with Metastatic Follicular Thyroid Cancer and the Possible Association of These Entities with McCune Albright Syndrome
S. Zaheer, A. Padhy, A. Goh
Nuclear Medicine and PET, Singapore General Hospital, Singapore
This is the pictorial depiction of a case report that centers on the unusual finding of ethmoid fibrous dysplasia in a patient with metastatic thyroid carcinoma and the possibilities associated with this finding. The happy outcome with regards to the metastatic thyroid cancer is shown. In summary, the course of thyroid carcinoma and incidentally associated fibrous dysplasia is depicted, and imaging findings on MRI, CT scan, bone scan, and I-131 whole body scans are described. Possible association with McCune Albright Syndrome is discussed. The patient is a 65-year-old lady with follicular cancer of thyroid gland. She initially had subtotal thyroidectomy followed by I-131 therapy for remnant ablation (as she declined completion thyroidectomy). Post-therapy whole body I-131 scan after remnant ablation revealed intact right thyroid lobe showing good radioiodine uptake. The serum thyroglobulin (Tg) level at that time was estimated to be 82.8 mg/L. In the presence of significant residual thyroid tissue, no functioning metastatic lesions were noted in the post-therapy scan. Six months later, the patient's suppressed Tg remained high and she was subjected to another high dose I-131 treatment and stimulated serum Tg testing to assess the functional status of the thyroid cancer. The post-therapy whole body scans showed complete ablation of the previously noted residual thyroid tissue in the neck, but revealed the presence of bilateral thoracic metastases. A Tc-99m MDP bone scan was performed to assess for any bone metastases. This revealed intense focal uptake of radiotracer tracer in the ethmoid region at the skull base. There was diagnostic dilemma, as the post-therapy I-131 scan results and the bone scan appearance were incongruent. Around this time, she gradually developed weakness and unsteadiness of both lower limbs, causing difficulty in walking. MRI brain and cervical spine in November 2005 was performed and this showed a 2.4 cm left ethmoid sino-nasal soft tissue mass, suspicious for a tumor. This corresponded to the uptake of tracer on the bone scan. To investigate this further, contrast CT of paranasal sinuses was done and this showed a mass expanding the non-pneumatized left posterior ethmoids, consistent with fibrous dysplasia. Subsequently, the patient was treated with successive doses of I-131 amounting to a total dose of 500 mCi in two separate sittings, resulting in complete ablation of functioning metastases and normalization of stimulated serum Tg level from 49.5 to 3.7 mg/L. Fibrous dysplasia, when associated with thyroid carcinoma, may cause diagnostic confusion. It may be a part of McCune Albright Syndrome. A combination of radiological, biochemical, and radionuclide investigations and therapeutic measures may help in comprehensive and appropriate management of such cases.
The Value of PET/CT in the Diagnosis and Therapy of Thyroid Cancer
E. A. Barrenechea, P. Bautista, J. Y. Santiago
Department of Nuclear Medicine and PET, St. Luke's Medical Center Quezon City, Philippines
Aim: It is generally known that PET imaging is unnecessary in patients with differentiated thyroid cancer because we have radioiodine scans and thyroglobulin determinations. Besides, PET/CT imaging has a low sensitivity for the thyroid gland. However, progressive dedifferentiation of thyroid cancer cells leads to a loss of iodine-concentrating ability, with resultant false-negative, whole body radioactive iodine scans in approximately 20% of all differentiated metastatic thyroid cancer lesions. It is the aim of this paper to look closely on where PET/CT is of value in thyroid diseases, especially in thyroid cancer.
Materials and Methods: A retrospective study was done reviewing all PET, PET/CT scans requested for thyroid diseases for the year 2005-2012. We tabulated results of PET/CT, TBS, serum thyroglobulin, USG, serum calcitonin, and clinical records, including the various therapies they underwent.
Results: Of 170 FDG-PET scans on 105 patients done between 2005 and 2012, were analysed. Their ages ranged from 17 to 83 years. The indications were as follows: 116 were requested to determine recurrence, 6 for staging, 11 for residuals, 21 for response to therapy, and 13 for monitoring. There were 77 cases of papillary thyroid cancer, 9 follicular thyroid cancer, 11 medullary, 2 anaplastic, 2 insular, 2 squamous, 1 adenosquamous, and 1 Castle disease. Majority of those requested was for differentiated thyroid cancer after surgery and radioiodine ablation, who had negative diagnostic I-131 whole body scans during routine follow-up, but with increasing serum thyroglobulin, as well as in problematic thyroid cancer cases. There were 32 cases of papillary thyroid cancer and 4 follicular TCA with increased thyroglobulin and negative I-131 scan with positive PET. Fourteen cases of PTC showed negativeI-131 scan, normal Tg, but three positive PET scans. The most frequent sites of metastases found in PET were in the neck area, the cervical lymph nodes, pretracheal nodes, and lungs. It is able to detect significantly more tumor sites than any imaging procedure. These data showed that the PET/CT findings led to a change to more appropriate clinical management of these patients with further surgical resection or lymph node dissection, gamma knife, external beam radiation, chemotherapy, and increased doses of RAI. Other uses of PET in our review of thyroid cases were for cytopathologically indeterminate thyroid nodules (3 cases), in calcitonin-positive patients (medullary thyroid cancer), although 18 F-DOPA is superior to FDG as one case was negative in PET, anaplastic cancer of the thyroid, and insular variety, as seen in our study. They usually are intense on FDG-PET and showed multiple sites of metastases in the spine, ribs, pelvis and lungs.
Conclusion: FDG-PET scans' greatest value is in the diagnosis and treatment of patients with negative I-131 body scans, but with increased thyroglobulin, as well as in the follow-up of difficult-to-treat and aggressive varieties and undifferentiated thyroid cancer. Their impact is in giving the appropriate treatment leading to better cure and survival.
Radioiodine Treatment for Thyrotoxicosis in Childhood and Adolescence: Treatment and Outcome
S. Namwongprom, S. UnachaUa-apisitwong, M. Ekmahachai
Radiology, Faculty of Medicine, Chiang Mai University Chiang Mai, Thailand
Objective: The aim of the present study was to evaluate the radioiodine treatment outcome of thyrotoxicosis in childhood and adolescence.
Materials and Methods: This was a retrospective study of 27 patients (age 7.2-19.8 years) with the diagnosis of thyrotoxicosis, who received I-131 treatment in Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chiang Mai University, from January 2007 to December 2011. Gender, duration of antithyroid drug (ATD) treatment, 24-h I-131 uptake, thyroid weight, the dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded.
Results: The outcomes of 27 patients (85.2% females and 14.8% males) treated with radioactive iodine therapy were analyzed to assess the effectiveness of therapy as related to dose and gland size. All children and adolescents were treated with 150 mCi of I-131/g of thyroid tissue (n = 27); at 6 months after treatment, 44.5% were hyperthyroid, 14.8% were euthyroid, and 40.7% were hypothyroid. Among 12 cases with hyperthyroidism, 2 cases needed the second dose of I-131 treatment and finally reached hypothyroid state. Patients were classified into two groups: treatment success (euthyroid and hypothyroid) and treatment failure (hyperthyroid). There were no significant differences of age, gender, duration of ATD treatment, 24-h I-131 uptake, thyroid weight, and I-131 dose between two groups (P < 0.05).
Conclusion: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence, with 55.6% treatment success. It is suitable as a good second-line therapy for patients with failure to medical treatment, severe complications, or poor compliance.
Follow-up of High-risk Thyroid Cancer Patients with Bone and Lung Metastases
R. Morales, R. Cano, L. Rivera, D. Moscol
Nuclear Medicine, Instituto Peruano de Energía Nuclear, Lima, Peru
Objective: The objective of the present work was to analyze the outcome of high-risk thyroid cancer patients after treatment with oral iodine 131.
Materials and Methods: Low-income patients in Peru often come to the institute with advanced disease and have to receive several doses of the radioisotope. Inclusion criteria were differentiated thyroid carcinoma, possibility of follow-up and data in the clinical file, lung or bone metastases, and having received more than 120 mCi (4.44 GBq). Exclusion criteria were lack of data in the files, geographic impossibility of follow-up, lost to consultation for more than 1 year, and doses less than 4.44 GBq. All patients had thyroglobulin measured in serum at each visit, and new therapy was decided according to results.
Results: Twenty-four thyroid cancer patients submitted to total thyroidectomy were followed up for more than 4 years after being treated with iodine 131, in the hospital wards. Eleven patients had lung metastases only, three had only bone metastases, and nine had bone and lung metastases, and two had multiple metastases (bone, lungs, axillary, hepatic, and mediastinal). Twelve patients responded favorably to therapy and are actually free of disease. Two patients had a partial response and have viable disease at present. Ten patients did not respond to therapy and of them, three have died. One patient who had a good outcome died from pulmonary disease not related to cancer. The non-responders had bone and lung metastases in eight cases and multiple metastases in the other two. Bone metastases were lytic in all cases. There was a case of calcaneal metastases and other of axillary involvement, which are rare forms of distant disease. The responder group received one or two doses of iodine 131, having several increasing doses in the non-responders. The highest accumulated dose was 1070 mCi (39.59 GBq), after an interdisciplinary decision to continue treatment. This patient is alive, with mediastinal disease.
Conclusions: It is concluded that response to iodine occurs when it appears early during treatment and that having multiple metastases is an unfavorable indication for response to this.
Low-dose Radioiodine Ablation for Differentiated Thyroid Carcinoma: A Retrospective Analysis
D. Nanayakkara, S. Herath, A. Galliyada
Nuclear Medicine Unit, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
Background: Differentiated thyroid carcinoma (DTC) is one of the most common cancers in the world, where the basic treatment strategy is well established. Total or near-total thyroidectomy as the standard initial treatment followed by radioactive iodine (RAI) therapy results in very good prognosis. RAI therapy is used as a postoperative ablation of residual thyroid tissues in high-risk patients with or without metastases to decrease the risk of recurrence. However, lack of inward facilities for RAI therapy has become one of the most important medical issues in Sri Lanka because the number of thyroid cancer patients has increased in the recent past although RAI therapy facilities and the number of available beds remain the same. Hence, the waiting time for RAI therapy has become 1-2 years. This situation is of much concern for patients with distant metastases who need early and high-dose RAI administration for a better prognosis. In order to reduce the waiting time, our unit practices giving low-dose (30 mCi) ablation on outpatient basis until the patients achieve complete ablation.
Aim: The aim of this study was to assess the therapeutic outcome of outpatient treatment with low-dose RAI in the management of DTC.
Materials and Methods: The study sample comprised DTC patients who were referred to our unit between January 2006 and December 2011 for radioiodine ablation or whole body scan (WBS) to assess the thyroid metastases. All patients had undergone total or near-total thyroidectomy before RAI administration. These patients had endogenous TSH stimulation 4-5 weeks after surgery and 30 mCi RAI was given at TSH over 30 mIU/l. Measurement of serum thyroglobulin (Tg) was done under TSH stimulation before therapy. Patients were given residual ablation dose (30 mCi; which is the maximum outpatient limit for our country) within 1-2 months postoperatively. Routine WBS or post-therapy scan (PTS) was obtained 6-7 days after oral administration of RAI. A standard WBS was performed using a medium-energy collimator, both anterior and posterior views. An additional neck scan was obtained using the pinhole collimator to assess the thyroid bed. Patients with significant residual thyroid tissues after 30 mCi were recalled after 6 months for a diagnostic WBS using 3-5 mCi of RAI. WBS was performed after 48 h. Patients with no residual neck uptake and serum Tg less than 5 ng/ml were considered as successful ablation. They were asked to restart levothyroxin and follow-up with annual serum Tg. Patients with significant thyroid residual and serum Tg over 5 ng/ml were given second dose of RAI and re-scan was done. This procedure was repeated until there was no residual thyroid tissue or serum Tg was less than 5 ng/ml. Patients who had lymph node (LN) or bone metastases at the time of surgery were referred for high-dose therapy. Patients who received RAI more than >100 mCi from other institutions and received neck radiotherapy before RAI therapy were excluded. The study relied on information obtained as part of routine clinical work and from the Nuclear Medicine Unit (NMU) database. All patients were given written information on RAI including radiation exposure to the general public and relatives. Informed consent was obtained. WBS or PTS was interpreted by an experienced Nuclear Medicine physician.
Results: From January 2006 to December 2011, totally 487 patients with DTC who had undergone total or near-total thyroidectomy in our hospital or in other hospitals were referred to our NMU in University of Peradeniya for RIA therapy or whole body metastatic evaluation. Average age of this study group was 42.4 years (Mode 38 years; range 10-81 years). The sex ratio was F: M =7:1. Of them, 150 patients received 30 mCi and 337 patients received 3-5 mCi whole body dose during this period. Common histology type was papillary carcinoma (75%); follicular carcinoma (15%), follicular variant of papillary carcinoma (8.8%), and Hurtle cells variety was (1.2%). Of the 150 who received 30 mCi of RAI, 37% (56/150) showed no residual, LN or bone metastases and were considered as successfully ablated. 6.6% (10/150) received second dose, and 4% (6/150) received third dose; 1.3% (2/150) patients received four doses and 2% (3/150) received five doses during this period to achieve complete ablation. Totally 51% (77/150) were ablated using 30 mCi, including multiple doses. The remaining 71 patients who revealed significant neck uptake but with serum Tg less than 5 ng/ml were considered as low-risk patients. They were advised to take thyroxin and monitor their serum Tg level. Two patients who had Tg over 50 ng/l were referred to oncology unit for high-dose therapy. Of all these patients, no one had positive LN or bone metastases. It is also noted that all these patients are still alive and free of disease. Radioiodine remnant ablation after near-total or total thyroidectomy is a key element in the management of patients with DTC. Early RAI after total thyroidectomy has shown very good prognosis. In the absence of adequate inward facilities, there is unavoidable delay in treatment. These results showed that one-third (51%) of the DTC patients treated with 30 mCi on outpatient basis were successfully ablated. Therefore, when facilities are inadequate, this method can be used as an alternative to treat DTC patients with low risk, rather than keeping all in a routine waiting list. It also facilitates to identify those are at risk and need high-dose therapy. They can be given priority without undue delay. Low-dose ablation minimizes unnecessary radiation to the low-risk patients and also preserves that radioiodine for patients who need to be rated with large doses. DTC is one of the cancers which could be successfully treated if detected and treated appropriately in time. When there are no inward facilitates, it is justified to use 30 mCi single or multiple doses 6 months apart on outpatient basis to identify low-risk group and ablate them as early as possible. This way, we can use the available inward facilities for patients who need high-dose therapy and minimize the waiting time for high-risk patients with LN or bone metastases.
Conclusion: In the absence of adequate facilities for radioiodine therapy, use of 30 mCi is justified for low-risk group. Use of multiple doses 6 months apart on outpatient basis and monitoring with serum Tg is useful.
Clinical Outcome of Radioactive Iodine Therapy Among Patients with Hyperthyroidism in St. Luke's Medical Center, Philippines
I. Bandong, J. Mendoza, E. A. Barrenechea
Department of Nuclear Medicine, St. Luke's Medical Center, Quezon City, Philippines
Background: Success rates in the use of radioactive iodine (RAI) therapy for hyperthyroidism have been variable in different parts of the world. Institutional studies have shown elimination of hyperthyroidism in 63.0% of cases in Princess Margaret Hospital in Hong Kong, 96.0% in the University of Cologne in Germany, 86.0% in Queen Elizabeth Hospital in the United Kingdom, 71.0% in St. Boniface General Hospital in Canada, and 86.0% in Brigham and Women's Hospital in the United States.
Objective: To determine success rate of RAI therapy for hyperthyroidism in the St. Luke's Medical Center-Quezon City (SLMC-QC).
Design: Descriptive, retrospective study.
Materials and Methods: A chart review of hyperthyroid patients who underwent RAI therapy from January 2010 to February 2011 and had follow-up thyroid function tests from 6 to 12 months post-therapy was done. Primary outcome measure is the rate of euthyroid or hypothyroid state. Demographic characteristics, clinical manifestations, baseline and follow-up thyroid function tests were obtained. Data were encoded and tallied in SPSS version 10 for windows. Descriptive statistics were generated for all variables. Fisher's exact test was used to determine the difference in the success rate of RAI therapy among different institution. A P value of less than 0.05 is considered statistically significant.
Results: A total of 22 patients were included. There were 6 males and 16 females with mean age of 40.80 years. Mean dose of radioactive iodine received was 14.4 ± 7.53 mCi. Mean follow-up period was 222.13 ± 83.52 days. Six of the 22 patients (37.5%) experienced persistent/recurrent hyperthyroidism and 16 (63.6%) attained either euthyroid or a hypothyroid state. Using Fisher's exact test, there were no statistically significant differences between our success rate at St. Luke's Medical Center and the above-mentioned experiences in different foreign institutions.
Conclusion: The practice of RAI therapy in St. Luke's Medical Center for hyperthyroid patients is at par with the experiences of other institutions worldwide. This success rate is comparable to the reported success rates in the above-mentioned institutions.
Hurthle Cell Carcinoma: The Nuclear Medicine Specialist Point of View
A. Ugrinska, D. Miladinova, B. Crcareva, L. Ivkovski, D. Bergant
Institute of Pathophysiology and Nuclear Medicine, Skopje, Macedonia
Hurthle cell carcinoma (HCC) is an unusual type of differentiated thyroid carcinoma (DTC) that accounts only for 3-5% of all the cases of differentiated thyroid neoplasms. This type of cancer is classified by WHO as a subtype of follicular thyroid cancer, considered as a separate entity due to its more aggressive behavior. Owing to very low incidence of this cancer, there are still no unified recommendations for the treatment of disseminated HCC. The treatment of choice for HCC is surgery. External beam radiotherapy can be administered after surgery when only R1 or R2 resection is possible or in the cases where surgery cannot be performed. Considering the very high percentage of radioiodine-negative tumors in this group of cancers, radioiodine is considered a treatment modality with limited potentials in patients with HCC. In this report, we present a case of a 68-year-old female patient with HCC that during the evolution of the disease developed radioiodine-negative cervical lymph node metastases and radioiodine-positive distant solitary metastasis in the right shoulder. The role of radioiodine therapy is further reviewed. Examination and ultrasound revealed multinodular goiter with two big nodules larger than 5 cm in both thyroid lobes during the first consultation of the patient at the Institute of Pathophysiology and Nuclear Medicine in Skopje. Fine needle aspiration biopsy (FNAB) was in keeping with Hόrthle cell adenoma with cellular atypia. Near-total thyroidectomy was performed. The pathological findings were in concordance with Hurthle cell adenoma bilaterally. Shortly afterward, the patient presented with nodes at the right side of the neck. Also, she reported pain in the right shoulder. Lymph node sampling was undertaken and the diagnosis of metastatic spread of Hurthle carcinoma was confirmed. Ablative radioiodine therapy with 3.7 GBq was administered. There was uptake in the thyroid bed and in the right shoulder. Second radioiodine therapy of 6.85 GBq was administered after 6 months. This time there was uptake only in the right shoulder. After both courses of radioiodine, there was good palliative effect with reduction of the pain in the right shoulder. Shortly after the second radioiodine therapy, new nodes in the right neck region appeared and the patient underwent modified radical right lymph node dissection of compartments II-V at the surgical department of the Institute of Oncology, Ljubljana. The dissection of the compartment VI was omitted due to negative US and left-sided recurrent nerve palsy after the first thyroid operation and dissemination of the disease. Histology revealed metastases in eight lymph nodes, with extension into fat tissue around. Operation was declared R2 also as a result of HCC dissemination. Metastatic right shoulder tumor was operated at the Orthopedic Clinic of University Clinical Center in Ljubljana. Histology revealed complete resection of the metastatic tumor. Third radioiodine therapy with 5.5 GBq and external beam radiotherapy of the neck are scheduled for the patient. If there is further progression of the disease, dedifferentiation therapy or tyrosine kinase inhibitors might be considered. Although there are still controversies on the use of radioiodine therapy in HCC, most authors agree that thyroid remnant ablation should be performed after extensive surgery. This approach makes the follow-up easier, and also might have some therapeutic benefits. According to our experience, if there is recurrent or metastatic disease despite the reports of very low percentage of radioiodine positive HCC, therapy with radioiodine should be considered.
Role of Serum Thyroglobulin Level and Whole Body Scan after 131 -I Therapy in Patients with Differentiated Thyroid Cancer
S. K. Biswas, F. Sultana, S. Hossain, F. Rahman, R. Begum, S. Hossain
Department of Nuclear Medicine and Ultrasound, Centre for Nuclear Medicine and Ultrasound, Bangladesh Atomic Energy Commission, Dhaka, Bangladesh
Background: Total thyroidectomy followed by 131 I ablation is the initial treatment most often used in patients with well-differentiated thyroid cancer. The thyroglobulin (Tg) level obtained 6-12 months after radioiodine ablation under thyroid stimulating hormone (TSH) stimulation is regarded as a very good prognostic indicator and is very important for clinical management. 131-I whole body scan (WBS) after radioiodine therapy plays a pivotal role for evaluating disease recurrence. This retrospective study was designed to unravel the impact of Tg level and 131-I WBS in clinical management of post-therapy patients with differentiated thyroid cancer.
Materials and Methods: Fifty patients (M: 11, F: 39) with differentiated thyroid cancer (papillary carcinoma: 42, follicular carcinoma: 8) were enrolled for this study during the period of July 2009 through July 2012. Tg level was checked before radioiodine therapy (Tg1) and at 6 months interval (Tg2). WBS was performed at 1 year interval for 2 years of radioiodine therapy and usually not done further if Tg level did not increase or there was raised suspicion of loco-regional tumor recurrence by ultrasonography or distant metastasis. Tg level was measured by immunoradiometric assay with a detectable limit of <0.01 ng/ml. Thresholds of 30 ng/ml and 10 ng/ml were considered for Tg1 and Tg2, respectively. PET-CT scan was recommended while Tg level was increased but WBS was negative. Second or third dose of radioiodine therapy was applied whenever required.
Results and Observations: All patients showed normal Tg level before radioiodine therapy. At 1 year follow-up, Tg level was normal and WBS was negative in 32 patients, Tg level was increased and WBS was positive in 8 patients, Tg level was normal but WBS was positive in 9 patients, and 1 patient showed raised Tg level but negative WBS. At 2 years follow-up, 41 patients showed normal Tg level and WBS results, both were positive for 6 patients, normal Tg but WBS was positive in 1 patient, and 2 patients showed increased Tg level but WBS was negative. Considering the cost, out of last two patients, PET-CT scan was possible for one patient and the result was positive. Second dose of radioiodine therapy was needed in seven patients and third dose was needed in six patients.
Conclusions: Post-ablative Tg levels and WBS played significant role for the management of differentiated thyroid cancer. Moreover, in a case of discordance between Tg level and WBS, PET-CT scan appeared to be a very useful adjunct to determine the dedifferentiation of thyroid cancer, which indicated a worse prognosis of the patient.
Potential Response of Graves' Disease Associated with Thymic Hyperplasia after Radioactive Iodine 131 Therapy
A. G. Mendoza Bonan
Department of Nuclear Medicine, Mary Mediatrix Medical Center, JP Laurel Highway, Lipa City, Philippines E-mail: firstname.lastname@example.org
A 49-year-old male diagnosed with Graves' disease presenting with an anterior mediastinal mass is reported. A chest X-ray examination showed a widened mediastinum with a consideration of an anterior mediastinal mass. Computed Tomography (CT) examination revealed an anterior mediastinal mass attributed as thymus gland hyperplasia of about 1.6 cm × 4.0 cm × 4.5 cm. No discrete nodularities and no compression of vessels were observed; no enlarged mediastinal or hilar lymph node was noted. The patient underwent radioactive iodine therapy. A repeat CT scan with contrast showed complete regression of the anterior mediastinal mass after treatment with radioactive iodine 131. The possible ablative effect of radioiodine therapy must be considered before subjecting the patient to unnecessary surgical procedure, e specially if significant regression of mass is noted and malignancy suspicion is ruled out.
Effectiveness of Radiation Synovectomy with Yttrium (90Y) Citrate Related to Preexisting Radiological Damage in Rheumatoid Arthritis Patients
B. Ajdinovic, L. Jaukovic, Z. Andjelkovic, S. Dugonic
Institute of Nuclear Medicine, Military Medical Academy, Belgrade, Serbia
Background: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Radiosynoviorthesis (RS) may be indicated in RA patients with persistent synovitis not responding to anti-rheumatic drugs and/or intra-articular glucocorticoid therapy.
Aim: The aim of this study was to evaluate the effects of 90Y citrate radiosynovectomy of the knees related to preexisting radiological damage in RA patients.
Materials and Methods: One hundred and ten patients (155 knees) with chronic knee synovitis and RA (according to the American College of Rheumatology criteria) participated in study. Radiography of the knee was performed at study entry and clinical evaluation was done at entry and at follow-up visits at 6, 12, 24, 36, and 60 months after treatment. Functional status (classes I-IV) and radiologic status (stages I-IV) were determined according to the Steinbrocker criteria. An exclusion criterion was Steinbrocker radiologic stage IV. Yttrium (90Y) citrate was administered into the knee, after aspirating synovial fluid, followed by immobilization of the knee. Therapeutic effects were assessed using clinical evaluation (the patient's and physician's global assessment of the effect of therapy joint pain, swelling, and the range of motion). Effects were classified as successful therapy (A), partially successful (B), failure (C), and considered as positive (A, B) and negative (C). For the analyses of therapeutic effects in different groups, P values less than 0.05 were considered statistically significant.
Results: Mean disease duration was 8-9 years, while mean duration of arthritis of the knee was 45 months. Steinbrocker radiological class at study entry was class I in 10.3%, class II in 69.6%, and class III in 20.1% of patients. At 12 months, effect A occurred in 77% of class I, 61% of class II, and 22% of class III joints. Positive effect was shown in 100%, 87%, and 44% of joints of stage I, II, and III, respectively. During the follow-up period of 5 years, positive effects in joints of Steinbrocker radiological stage I and II remained stable. On the other hand, at the end of follow-up period, there were no more joints of stage III with positive effect. Clinical effect was significantly different between the groups (I + II) and III (P < 0.001).
Conclusion: Clinical efficacy of synoviorthesis using 90Y-citrate in RA-diseased knee joints was related to radiological stage. The positive effect of RS in patients with radiological stage III might be attributed to functional status of moderate disease activity.
Treatment Efficacy of Sm-153 Lexidronate for Pain Management of Bone Metastases: The First Experience in Iran
N. K. Ayati, R. Zakavi, K. Aryana, F. Homaee, A. Bahrami-Samani
Department of Nuclear medicine, R Mashhad University of Medical Science Research Center, Mashhad, Iran
Background: Involvement of the skeleton can cause excruciating pain in two-thirds of terminal patients with history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy, and external beam radiotherapy, bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Such therapies have several advantages, including the ability to treat multiple sites of tumoral involvement simultaneously, no significant conflict with other treatments, ease of administration, and the potential to be used repetitively. But in Iran, use of this modality is not widely practiced. In this study, we evaluated the clinical usefulness of Sm-153 lexidronate for pain management of bone metastases.
Materials and Methods: Twenty-eight patients (14 males and 14 females) aged 38-77 years with the history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had recent whole body bone scan indicating multiple bone metastases. The patients received intravenous injection of 1 mCi/ kg Sm-153 lexidronate. Whole body scintigraphy was done 3 or 18 h post-injection. Pain relief and quality of life were evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every 2 weeks. Active follow-up was performed.
Results: 46% of patients showed presence of flare phenomenon during the first 4 days after Sm injection with mean duration of 1.7 days. The pain relief began between 2 and 16 days post-injection and the duration of pain palliation was in the range of 4-32 weeks (mean ± SD = s15.22 ± 7.8). 64% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Overall response to therapy was 85.7%.) The lowest amount of peripheral blood cells was detected in the second week for WBCs and RBCs and in the fourth week for platelets. No one experienced hematological toxicity induced problem.
Conclusion: Sm-153 lexidronate is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved.
Clinical Characteristics, Efficacy of Treatment and Outcome of Patients with Differentiated Thyroid Cancer with Bone Metastases: A Retrospective Study
S. T. Butt, F. Shazia, N. Wajiha, J. Ghazal, I. Javaid
Department of Nuclear Medicine, Nuclear Medicine Oncology and Radiotherapy Institute, Islamabad, Pakistan
Background: Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer (DTC). Prognosis and outcome of these patients is unfavorable.
Objectives: To investigate the clinical efficacy of (131) I therapy in patients with bone metastases from DTC and to assess their prognosis and survival.
Materials and Methods: We reviewed medical records of 360 patients of DTC treated in our institute from 2000 to 2005. Manifestations, treatment, and clinical outcomes of 57 patients who had differentiated thyroid carcinoma with bone metastases were studied. We analyzed those patients with regard to clinical characteristics, treatment, prognosis, and survival.
Results: Incidence of bone metastases from thyroid carcinoma in patients treated at NORI during the period 2000-2005 was 15.8%. Male patients were 15.3% and females were 84.6%. Histopathologic subtypes included papillary (44%) and follicular (56%). Multiple sites of bones were involved in 50% of patients. Single bone site was involved in 29%, while 20.8% of the patients had metastasis to other organs in addition to bone. Patients presenting with bone metastasis were 52%, while 47.3% patients were found to have bone metastasis during baseline investigations. All patients underwent near-total thyroidectomy followed by aggressive radioiodine therapy. Number of 131 I doses received ranged from 3 to 12 with a mean of 6.6. Mean dose of I131 per patient was 48,914 MBq ± 20,424 (range: 18,130-76,960). Baseline thyroglobulin (TG) level ranged from 380 to 17,300 ng/ ml, with a mean value of 2250 ng/ml ± 5644. Sixty percent of patients showed declining trend in TG over time, while 23% of total patients showed rising trend and 6.2% of the patients had normal TG/ATG (antithyroglobulin) values throughout the course of disease. Also, 48-56% drop in TG level (as a fraction of total drop in TG) occurred after first dose of I131 therapy. 81% patients reported symptomatic improvement and 19% patients had no relief of symptoms. Five year survi val was observed in 64% of the patients with bone metastasis.
Conclusion: Multiple bone metastases represent a frequent complication of DTC, especially of follicular thyroid cancer. Prognosis and survival is good in the patients with bone metastasis if they are managed with high first I131 dose, and repeated radioactive iodine therapies after total thyroidectomy.
Production, Quality Control, and Biological Evaluation of 153 Sm-isoPDTMP and 153Sm-TTHMP as a Sent
Z. Naseri, A. R. Jalilian, A. Nemati Kharat
Department of Chemistry, University of Tehran, Tehran, Iran
Radionuclides have been used to treat skeletal diseases for decades. At present, an array of radionuclides has been proposed for treating bone pain due to cancer. The most promising among these radionuclides is 153Sm. This radionuclide has favorable radiation characteristics: t1/2 = 1.93 d; bmax = 0.81 Mev (20%), 0.71 Mev (49%), 0.64 Mev (30%); and g = 103 Kev (30%) emission, which is suitable for imaging purposes during therapy. Various bone palliative therapeutic agents have been developed for bone metastases, such as 153Sm-EDTMP which is widely used. EDTMP has been proven to be a good therapeutic agent for the treatment of pain due to skeletal metastases and is now commercialized. In this study, production, quality control, and biodistribution studies of a newly developed therapeutic compound will be presented, followed by imaging studies in wild-type rodents. 153Sm-isoPDTMP and 153Sm-TTHMP was prepared starting with 153Sm-SmCl3, prepared by neutron activation of an enriched 152Sm sample (purity >98%), and in-house synthesized TTHMP and isoPDTMP (amine: 1,2-diaminopropane) in 1 h at 25°C, followed by stability tests, partition coefficient determination, and biodistribution studies in wild-type rodents using scarification. The radiolabeled Sm complex was prepared in high radiochemical purity (>99%, ITLC) and specific activity of 278 GBq/mmol, and demonstrated significant stability at 4, 25, and 37°C (in the presence of human serum). The obtained results of this work were compared with 153Sm-EDTMP data that exhibited favorable results. Initial biodistribution data showed significant bone accumulation of the tracer in 48 h. The properties of the produced 153Sm-isoPDTMP and 153Sm-TTHMP suggest an efficiently new bone palliative therapeutic agent in order to overcome the metastatic bone pains.
Effectiveness of Strontium-89 Therapy in Multiple Bony Metastases Patient with Breast and Prostate Cancer
O. P. Sinha, M. Mayank, R. Tiwari, S. Rachch, V. Patel, V. N. Bhatt
Department of Nuclear Medicine, Gujarat Cancer and Research Institute, Ahmadabad, India
Background: Sr-89 is an effective alternative for the treatment of bone pain in patients with painful skeletal metastases. It is a beta-emitting radionuclide that localizes in area of active bone formation. It functions as calcium analog that releases high-energy beta particle as the compound decays to yr-89.
Objective: We aimed to determine the benefits and complications of Sr-89 therapy and to evaluate the pain response and daily discomfort in patients with painful bone metastases treated with Sr-89.
Materials and Methods: Bone scans of all 70 patients were done before and 2 months post-therapy with the help of dual-head gamma camera. Those who showed multiple bony metastases had been treated with 4 mci fixed dose Sr-89. Patient age range was 34-71 years; 30 patients were known case of carcinoma breast and 40 were carcinoma prostate. Sr-89 was procured from POLATOM, Poland. Blood count, intensity of pain, drug intake, life activity, and duration of effectiveness were evaluated in all patients on bimonthly basis for the first 2 months, and thereafter monthly.
Results: We evaluated the life activity on Karnofsky performance scale (KPS): 30 patients (43%) 70% KPS, 14 patients (20%) 80% KPS, 16 patients (23%) 40% KPS, and 10 patients (14%) 0-10% KPS. The mean decrease in platelets and leukocyte was 25-35%. Hemoglobin was reduced by only 10-20% of the baseline value. Most of the patients' pain killer drug dose reduced, except in poor performers. Pain relief duration was 3 months to 1 year.
Conclusion: This study suggests that Strontium-89 is a valuable therapy for palliation of pain from metastatic bone lesions. The drawback is the very high cost and availability.
A Study on Srontium-90 Irradiation for Treatment of Postoperative Conjunctival Squamous Cell Carcinoma
R. Hussain, K. K. Nath, S. Sultana, F. Alam, S. Afroz
Institute of Nuclear Medicine and Ultrasound BAEC, BSM Medical University Campus, Dhaka, Bangladesh
Background: Beta irradiation by strontium (Sr-90) has been in use for sometime in Bangladesh for the therapy of conjunctival squamous cell carcinoma (SCC). This retrospective analysis was performed to evaluate its efficacy and the risk and incidence of complications.
Materials and Methods: A retrospective analysis was done on 12 patients receiving postoperative beta irradiation from March 2009 to February 2012. There were 10 males and 2 females, with age ranging from 30 to 85 years with a mean of 50.7 years. Study group included seven well-differentiated, one moderately differentiated with infiltration, one verrucuous, and three SCC in situ. Each patient received 130 Gy to the postoperative sclera surface in five fractions by hand-held Sr-90 surface applicator. The patients were followed up at 1 week, 1 month, 6 months, and 1 year intervals after beta irradiation.
Results: Out of the total 12 cases, 11 had follow-ups for more than 1 year. None had recurrence within 1 year. Short-term complications included conjunctivitis, photophobia, watering of eyes, etc. As for long-term complications, one case developed cataract. The short-term complications were self-limiting and had no serious effect. One case having cataract was over 60 years old, so it could not be clearly understood whether the normal aging process or the radiation contributed more in the development of the cataract.
Conclusion: Sr-90 beta irradiation is effective and a safe treatment option for conjunctival SCC.
The Synthesis, Radiolabeling, and First Biological Evaluation of a New 166Ho-complex for Radiotherapy of Bone Metastases
S. Zolghadri, H. Yousefnia, A. Jalilian, A. Bahrami-Samani, M. Ghannadi-Maragheh, H. Afarideh
Nuclear Science and Technology Research Institute, Tehran, Iran
In this study, the 166Ho-triethylene tetramine hexa (methylene phosphonic acid) (166Ho-TTHMP) complex was prepared as a bone palliation agent. The complex was successfully prepared using an in-house synthesized TTHMP ligand and [166Ho] HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 n/cm 2 /s) of natural Ho (NO3) 3 samples followed by radiolabeling and stability studies. Biodistribution studies were also performed in wild-type rats. The complex was prepared with the specific activity of 3-5 GBq/mg and a high radiochemical purity >99% (checked by ITLC). The 166Ho-TTHMP complex was stable in the final preparation and in the presence of human serum (>90%) up to 72 h. The biodistribution of 166Ho-TTHMP in wild-type rats demonstrated significant bone uptake compared to 166HoCl3 up to 48 h. SPECT imaging of the radiolabeled compound demonstrated complete accordance with the biodistribution data. The major uptake was observed for long bones including thigh bones as well as skull and also knee and vertebrae. Primary properties of 166Ho-TTHMP demonstrate that this new therapeutic agent can be a good choice for metastatic bone pains.
Post-therapy Precautions and Imaging Properties of Samarium-153 versus Strontium-89
R. M. Goco, E. A. Barrenechea
Department of Nuclear Medicine, St. Luke's Medical Center, Quezon City, Philippines
Aim: To compare the post-therapy precautions and imaging properties between the bone palliation agents Samarium-153 and Strontium-89.
Materials and Methods: Patients with various bone metastases were subjected to either Samarium-153 or Strontium-89 in our department. We compared the post-therapy precautions that we give to the patients as well as the protocol for doing their respective post-therapy images.
Results: The most widely used radionuclide for bone palliation is Strontium-89 (Sr89), a radionuclide that is chemically similar to calcium and imitates its biodistribution. It was found that 70% of Sr89 is stored in bones and has a physical and biologic half-life of 50.5 and 14 days, respectively. The biologic half-life of Sr89 in tumors is longer than in normal bone due to its prolonged retention. Sr89 undergoes beta minus decay with a beta emission of 1.463 MeV. The maximum range is approximately 8 mm, which means that the greatest radiation dose is given to the cortical and trabecular bone, with minimal irradiation to adjacent soft tissue. It is primarily excreted through the renal/urinary tract and is greatest during the first 2 days post-administration. We included eight patients (six for Sr89 and two for Sm153). We had to instruct them regarding urine contamination and to increase their fluid intake during this time. They were asked to take analgesics in case of flare during the first 48 h and undergo weekly to biweekly CBC monitoring for 8-12 weeks. Since the gamma emission was less than 0.5%, the patients did not pose a radiation hazard, so we just confine them a day for the IV administration of both radiopharmaceuticals. It is also difficult to scan these patients, as it is more of a beta emitter; hence, we just did a Bremsstrahlung imaging. Head to mid-thigh images were acquired for 900 sec using the following parameters: Energy window 75 ± 30% keV, zoom 1×, and matrix size 1024 × 256. The efficacy in terms of bone pain relief was 65-75%, and complete relief was in the range of 20%. Patients may experience an increase in short and self-limited bone pain during therapy. The inhibition of tumor growth ameliorates pain and preserves mobility, thereby maintaining quality of life. With Samarium-153, the physical properties include 103 keV gamma emission. Sm153, however, is the only agent in its class targeted to bone via chelation to the aminotetraphosphonate EDTMP (ethylenediaminetetra-methylenephosphonic acid). The particle emissions from Sr89 and the corresponding ranges in bone and soft tissue are much greater than those of Sm153. Higher-energy particles are associated with greater marrow toxicity as a result of the larger volumes of marrow exposed to radiation. The shorter physical half-life of Sm153 (1.9 days) results in a more rapid delivery of radiation than Sr89 (50.5 days). The precautions we give to the patients during the therapy are the same as for Sr89. It is only in the post-therapy imaging they differ, wherein we get better images for Samarium. The biodistributions of Sm153-EDTMP and Tc99m-MDP are very similar in metastatic and normal bone; thus, bone scanning can be used for patient selection and follow-up.
Conclusion: Metastatic bone disease contributes significantly to morbidity and mortality of patients with advanced cancer, with a direct relationship evident between extent of bone involvement and survival. The radionuclide bone scan is the most reliable method of detecting bone metastasis in patients with various cancers, which is a pre-requisite to bone palliation therapy. We compared two radionuclides approved for treatment of bone pain, Strontium-89 and Samarium-153, each with differing bone targeting mechanisms. Both these agents were effective in all our patients in alleviating pain and reducing opioid use. The necessary precautions before and after therapy are the same. Gamma imaging of Sm153 appears better than Bremsstrahlung imaging of Sr89 in the follow-up and assessment to therapy response.
Semi-quantitative Estimation of Samarium-153 Therapy Results of Metastatic Bone Disease in Mono-regime: Regime and in Combined Treatment with Bisphosphonates
N. Rasulova, V. Lyubshin, D. Arybzhanov, D. Akhmedova, R. Karrer, A. Barttl, S. Wlodarczyk
Department of Nuclear Medicine, Republic Specialized Center of Surgery, Tashkent, Uzbekistan
Objective: To compare different regimes of bone metastases treatment by Samarium-153 oxabifore in mono-regime and in combination with zoledronic acid by using semi-quantitative analysis of diagnostic Tc99m MDP WB scans before and after Sm-153.
Materials and Methods: Fifty-four patients (43 females with breast cancer and 11 males with prostatic cancer; mean age 55 ± 9 years, min.- 29, max.- 76) with metastatic bone disease received Sm-153 treatment. Thirty-eight patients (I group) received Sm-153 oxabifore in combination with zoledronic acid and 16 patients (II group) received Sm-153 oxabifore in mono-regime. Diagnostic WB bone scans before and 6-12 months after therapy were estimated by program analyzing anterior and posterior views of WB bone scans and calculating percentage of bone tissue with osteoblastic metastases in each of four regions: 1- head and spine, 2- extremities, 3- pelvis, and 4- shoulders and ribs.
Results: According to semi-quantitative analysis of WB bone scans, 32 out of 38 patients (84.2%) in I group and 11 out of 16 (68%) in II group had statistically significant regression of bone metastases: mean total percentage of bone tissue involved in osteoblastic metastases reduced in first region from 54.9 ± 2.8% (min.- 22.1; max.- 96%) to 36.4 ± 2.7% (min.- 7.8%, max.- 88%; P = 0.0002); in second region from 16.8 ± 3.2% (min.- 0.2, max.- 92%) to 8.6 ± 2.2% (min.- 0.06%. max.- 74%; P = 0.03); in third region from 44.9 ± 3.4% (min.- 11.1, max.- 96.4%) to 24 ± 2.7% (min.- 3.6%, max.- 86%; P = 0.0001), and in fourth region from 31.9 ± 3.6% (min.- 2.2, max.- 95.9%) to 14.4 ± 2.2% (min.- 0.9%, max.- 65%; P = 0.0001). One patient (6.25%) from II group had no significant changes on comparing WB bone scans before and after treatment. Seven patients [3 from I group (7.8%) and 4 from II group (25%)] had progression of metastatic bone disease in one of the four regions and three patients (7.8%) from II group had simultaneously two processes-progression and regression of bone metastases; however, statistically the above-mentioned changes were not significant: In the first region, percentage of bone involvement in mats process changed from 46.3 ± 5.6% (min.- 27, max.- 51%) to 44.1 ± 5.2% (min.- 25%, max.- 58%; P = 0.7), in the second region from 11.0 + 6.3% (min.- 1.4, max.- 12.5%) to 13.2 + 5.4% (min.- 1.5%, max.- 21.9%; P = 0.7), in the third region from 33.6 ± 6.7% (min.- 21, max.- 54%) to 38.2 ± 6.4% (min.- 23%, max.- 64%; P = 0.9), and in the fourth region from 17.5 ± 3.9% (min.- 5.8, max.- 21.4%) to 22.9 ± 6.5% (min.- 6.5%, max.- 27.4%; P = 0.4).
Conclusion: According to semi-quantitative analysis of WB bone scans, there was statistically significant regression of osteoblastic bone metastases in 84.2% of patients who received combined therapy with Sm-153 oxabifore and zoledronic acid and in 68% patients who received Sm-153 oxabifore as mono-therapy. Progression of bone metastatic disease was found in 7.8% of patients from group I and 25% of the patients from the group II. Same number of patients (7.8%) from group I had simultaneously two processes: Regression and progression of bone metastases. One patient (6.25%) from II group had stabilization of metastatic bone disease.
Preparation and Biodistribution of 99mTc and 188Re Labeled Zoledronic Acid
O. Klementyeva, A. Malysheva, G. Kodina, V. Korsunsky, E. Rabinovich, L. Voloznev, V. Krylov
Department of Radiopharmaceuticals, Burnasian Federal Medical Biophysical Center, Moscow, Russia
Background: Bone metastasis is the most frequent manifestation of progression of prostate cancer, breast cancer, and lung and many other cancers. Pain and bone fractures greatly impair the life quality of patients and reduce their survival. Bisphosphonates (BP) are a very important class of osteotropic compounds. They are effective in treating benign and malignant skeletal diseases characterized by enhanced osteoclast-mediated bone resorption (i.e., osteoporosis, Paget's disease, and tumor-induced osteolysis). Zoledronic acid, a novel N-BP with an imidazole substituent, has demonstrated more potent inhibition of osteoclast-mediated bone resorption than all other bisphosphonates in both in vitro and in vivo models. Current knowledge of the pharmacology of N-BPs at the molecular level largely explains their observed effects on bone metabolism and tumor growth in animal models and their clinical activity in the treatment of benign and malignant bone diseases. 99mTc-technetium (99mTc) and 188Re-rhenium (188Re) represent an attractive pair of radionuclides for biomedical use because of their favorable decay properties for diagnosis (99mTc 6 h half-life, 140-keV g-radiation) and therapy (188Re: 17 h half-life, 2.12-MeV b-max-radiation) and because of their onsite availability, thanks to corresponding 99Mo/99mTc and 188W/188Re generator systems. The aim of this study was to investigate the influence of reaction conditions for the synthesis of 99mTc-ZA and 188Re-ZA complexes and describe their biodistribution in experimental animals.
Materials and Methods: Na99mTcO4 and Na188ReO4 were obtained from the generators produced by the Institute of Physics and Power Engineering (Obninsk, Russia). Zoledronic acid was synthesized in Pharm-Syntez (Moscow, Russia). The other chemicals were commercially produced (Merck). All animal experiments followed the principles of laboratory animal care. Female white rats of about 200 g body weight with and without bone pathology were used. The bone pathology was simulated by the closed femur fracture. Biodistribution of both radiopharmaceuticals was studied in with bone pathology in 10 days post-fracture model. About 0.2 mCi of 99mTc-ZA or 188Re-ZA was injected intravenously into each of the rats via the tail veins. After 10 days, the animals were sacrificed and dissected. The selected tissues were removed and the radioactivity was counted by a g-counter (Wizard 2480-0010, PerkinElmer LAS/Wallace) to determine tissue distribution of the radiotracers.
Results: Radiopharmaceutical composition of 99mTc-ZA with radiochemical purity >95% can be prepared using the ligand: SnCl2 molar ratio from 2.5 to 3.5 at pH 5.0-6.5 after incubation for 20 min at room temperature. The composition of 188Re-ZA can be prepared with radiochemical yield >90%. The composition was stable during 3 h from the moment of its preparation. The skeletal uptake of 99mTc-ZA was about 50%; the uptake ratios of bone-to-blood were more than 20 at 1 h and up to 100 at 5 h after injection, respectively. Differential coefficient of uptake (CDU) femur-to-femur with pathology was between 1.7 and 2.1. 188Re-ZA rapidly accumulates and is fixed in both normal femur bone and in bone pathology. The skeletal uptake was about 32%, the CDU bone-to-blood ratio was more than 4 at 1 h and 18 at 5 h after injection, respectively. CDU femur-to-femur with pathology was about 3.6. The preclinical trials with 188Re-ZA are completed and the clinical trials have begun now.
Radiopharmaceutical Based on Monopotassium Salt of Hydroxyethylene-diphosphonic Acid Labeled with Re-188 for Therapy of Bone Metastases
V. Petriev, V. Skortsov, V. Shiryaeva, V. Kanygin, V. Korsunsky, V. Oshchepkov, V. Krylov
Department of Radiopharmaceutical, Medical Radiological Research Center, Obninsk, Russia
Background: Bone metastasis is a very important issue in oncology at the present time. A lot of patients with breast, prostate, and other tumors have bone pain, fractures, and reduced quality of life. Derivatives of phosphonic acids are widely used for development of radiopharmaceuticals for therapy of bone metastases. Monopotassium salt of hydroxyethylene-diphosphonic acid (KHEDP) is one of these derivatives. Lyophilizate based on KHEDP for generator-produced 188Re was developed. It allows obtaining high-yield 188Re-KHEDP (no less than 95%) during 1 h just before administration to a patient. Due to its physical and nuclear properties for accumulation of therapeutic dose level in a tumor, 188Re is a very important radionuclide. In addition to that, Russia is the only country where industrial generator production of 188W/188Re is possible. The purpose of the study is to research into functional usefulness of 188Re-KHEDP in relation to uptake of the radiopharmaceutical in normal and tumor tissues.
Results: Investigation of pharmacokinetic characteristics of the radiopharmaceutical was carried out in intact rats and in rats with experimental callus on the femur bone. Three batches of the radiopharmaceutical were investigated. It was observed that the pharmacokinetics of radiopharmaceutical in all batches was the same; 188Re-KHEDP accumulated in the bone tissue mainly, especially in the callus, fast-growing tissue; it was eliminated from blood through the kidneys. The highest level of activity in the normal tissue and in the callus was achieved in 3 h after injection, i.e., 1.23-1.41 and 2.55-3.07%/g, respectively. Coefficient of differential accumulation of the radionuclide in the callus was 2.11-3.07 and persisted for 24 h.
Conclusion: 188Re-KHEDP is a functionally useful bone-seeking radiopharmaceutical; it is capable of retaining therapeutically absorbed dose for internal irradiation of a focus (callus).
Potential Role of Semi-quantitative Analyses of Bone Metastases in Evaluation of radionuclide therapy Response
N. Rasulova, R. Karrer, A. Bartl, Wlodarczyk
Department of Nuclear Medicine, Republic Specialized Center of Surgery, Tashkent, Uzbekistan
Objective: To create software for evaluation of bone metastases treatment efficacy by using whole-body bone scans before and after treatment.
Program: BoneMeta is a program for semi-quantitative analysis capable of calculating the percentage of bone- and soft-tissue uptake of radiopharmaceutical from the scan images. BoneMeta is fully written in MATLAB and is therefore available on all platforms using DIACOM files.
Operation Modes: There are two modes of operation in BoneMeta: Loading only two files, containing anterior and posterior of either diagnostic scans, or (after)-treatment scans, or loading four images, containing before and after treatment data (anterior and posterior). A dialog will appear where one can select the mode of operation and load the appropriate images. All file types of the common manufacturers (MEDISO, Philips, Siemens) are supported, as well as different image sizes. The more common are 256 × 1024 and 512 × 1024. By clicking on Proceed, the dialog will close and the images will be displayed in the main window. Position correction is done automatically. There are several views: Original Image-View on which it is possible to delete unnecessary region which should not be included for further proceeding and Bone Tissue-View is the area of the image representing the bone tissue. For a more detailed selection, one can manually add or remove portions of bone-tissue, Metastases-View similar to the Bone Tissue-view but now showing metastases. All views (original, bone, meta) are plotted on top of each other using different colors in an overlaying manner. Regions of Interest (ROIs): After loading images, the ROIs are shown in the leftmost image (anterior before treatment). They divide the body image into four score-areas: Head and spine, chest, pelvis, and extremities. Statistics Dialog: The button Statistics will bring up a new dialog with all the statistics and the function for calculating the bone- and soft-tissue-uptake. Export data: The data can be exported to EXCEL-readable CVS files creating a database. It is the medical scientist's responsibility to properly select the bone-tissue and the metastatic tissue. Considering one single ROI (e.g., pelvis), the area which makes an out bone tissue in this ROI is considered to be 100%. A representative value for this is the number of pixels of bone tissue in the ROI (CBT). The value representing the amount of metastases in the ROI is the number of pixels in metastatic tissue (CMT). These values are obtained by counting the number of pixels, whose values are above a certain threshold. This threshold is set by the user using the sliders below the images and is depicted also graphically. The percentage of abnormal tissue in the ROI (PAT) is thus calculated by: PAT = MT/CBT × 100. This is done separately for anterior and posterior images, and also a combined total percentage (PATT) is calculated where the number of pixels of anterior and posterior images are added: PATT = (CMTA + CMTP)/(CBTA + CBTP) × 100, where CMTA/P is the number of pixels abnormal anterior/posterior and CBTA/P is the counts of pixels in bone-tissue anterior/posterior.
Conclusion: BoneMeta program is designed to compare WB bone scans before and after treatment to estimate bone metastases treatment efficacy by semi-quantitative analyses. Probably this program can help in estimation of duration of flare pain period that already relies upon diagnostic scans. Using RezoscanTc99m which is based on Zoledronic acid and comparing it with Tc99m MDP, this program may show us percentage of blastic and mixed bone metastases and its treatment prognoses. If needed, we can adjust this program for other manufactures like GE DIACOM files.
Selective Internal Radiation Therapy using Yttrium-90 Microspheres: A Practical Demonstration of Personalized Artery-specific Dosimetric Modeling
Y. Toh, Y. H. Kao, A. E. H. Tan, D. C. E. Ng, A. S. W. Goh
Nuclear Medicine and PET, Singapore General Hospital, Singapore
Yttrium-90 (Y-90) selective internal radiation therapy (SIRT) (also known as Y-90 radio-embolization) via transarterial delivery of Y-90 microspheres is an emerging modality in the therapy of patients with inoperable liver tumors. Currently in many institutions, Y-90 SIRT activity planning is either based on semi-empirical body surface area estimates or planar Medical Internal Radiation Dosimetry (MIRD partition model), which have inherent limitations in safety and efficacy.The artery-specific SPECT/CT partition model is a personalized predictive dosimetric protocol designed, validated, and implemented by our institution in 2011. It allows for patient-specific dose calculations in Y-90 SIRT radiation planning, integrating catheter-directed CT hepatic angiography, Tc-99m-MAA SPECT/CT, and partition modeling for personalized predictive radionuclide dosimetry. We present a practical demonstration on how such personalized dosimetry can be performed, using freely available software solutions for region-of-interest (ROI) contouring, volume and count quantification, and how the data are used for predictive dosimetry. Compliance with radiobiologic principles of internal dosimetry is fundamental to Y-90 SIRT success. Image-guided artery-specific SPECT/CT predictive dosimetry allows for safe and effective Y-90 SIRT.
14-Production and Quality Control of [166 Ho]-DOTA-bevacizumab for Therapeutic Applications
A. Khorrami Moghaddam, A. Jalilian, K. Yavari, B. Bolouri, A. Bahrami Samani
Medical Physics, Tehran University of Medical Sciences, Tehran, Iran
Anti-angiogenic monoclonal antibodies in combination with therapeutic radionuclides are potential targeted therapy agents in cancer. In this study, bevacizumab was successively labeled with 166[Ho] HoCl3 after conjugation with DOTA-NHS-ester, with a radiochemical purity of higher than 95% (RTLC). The conjugates were puriﬁed by molecular ﬁltration, the average number of DOTA conjugated per mAb was calculated, and total concentration was determined by spectrophotometric method. The average chelate to antibody ratio (c/a) for the conjugate used in this study was 5.8:1 and protein integrity experiments (SDS-PAGE). The biodistribution studies in wild-type rats demonstrate a similar pattern to the other radiolabeled anti-vascular endothelial growth factor A (VEGF-A) immunoconjugate. 166Ho-DOTA-bevacizumab is a potential compound for therapy/i19aging of VEGF-A expression in oncology.
Assessment of Human Effective Absorbed Dose of 67Ga-ECC Based on Biodistribution Rat Data
H. Yousefnia, A. Jalilian, S. Zolghadri, S. Shanesazzadeh, H. Afarideh, F. Abassi-Davani
Nuclear Science and Technology Research Institute, Tehran, Iran
In this work, the radiation-absorbed dose of [67Ga]-ethylenecysteamine cysteine ([67Ga] ECC) to human organs was determined by using distribution data for rats. The spark method was applied to extrapolate the percentage of the injected dose in rats to humans. Then, the radiation-absorbed dose was determined by Medical Internal Radiation Dose (MIRD) method. The results show that the organs which receive the highest absorbed dose are kidneys and lungs, respectively. In this research, the absorbed dose of [68Ga] ethylenecysteamine cysteine was also calculated by the assumption that the biodistribution of ([67Ga] ECC) and ([68Ga] ECC) are the same. These radiopharmaceuticals can be good SPECT and PET tracers since they can be produced easily, and also the absorbed dose in each organ is less than the permitted absorbed dose given by Food and Drug Administration.
Radiation Safety Consideration in 90Y-Microsphere Therapy
A. Jha, A. Zade, V. Rangarajan, S. Shah, A. Agrawal, N. Purandare, N. Shetty, S. Kulkarni
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, India
Background: 90Y-microsphere radio-embolization is a multi-disciplinary therapeutic modality, which involves nuclear medicine and intervention radiology departments. The use of microsphere therapy is extensively reviewed in literature for various hepatic neoplasms. 90Y is a pure beta-particle emitting radioisotope that is incorporated in biocompatible microspheres. Two FDA (USA) approved commercial products are available in India at present. 90Y resin microspheres (Sirtex Medical) are polymer beads designed to be between 20 and 60 mm in diameter and loaded with 90Y at a specific activity of 40-70 Bq per sphere. 90Y Glass-Sphere (MDS Nordion) measures between 20 and 30 mm and is loaded with 90Y at a specific activity of 2400-2700 Bq per sphere. 90Y-microsphere therapeutic procedure is regulated and licensed by Atomic Energy Regulatory Board (AERB) in India. Primary licensee of 90Y-microsphere is a nuclear medicine physician and an intervention radiologist is authorized to administer the dose under the supervision of Radiological Safety Officer (nuclear medicine). There are no specific guidelines provided by AERB as such regarding carrying out the therapeutic procedure and radiation surveillance procedure, except for the patient discharge criteria. As per AERB guidelines, patient can be discharged immediately post-therapy if medically fit. In our hospital, we have drafted a separate radiation safety document for radiation survey during priming, administration, and post-administration, in addition to the checklist supplied by the vendor.
Aim: The aim of our study is to monitor radiation level during therapy, checking contamination if any, monitoring post-therapeutic dose rate from the patient body on the surface and at 1 m, estimation of percentage dose delivered, and ensure the safe handling of radiation waste generated.
Materials and Methods: Thirty patients who underwent 90Y-microsphere therapies for hepatic malignancies were monitored for radiation dose rate at body surface and at 1 m distance. The dose rate at a distance of 30 cm from unsealed vial, exposure rate at the surface of priming set vial loaded for administration, and dose rate at 4 cm from the connection of catheter and outlet tubing were measured. Readings ware also obtained after completion of infusion at anterior, left lateral, and right lateral positions on the abdomen surface of the patient. Dose rate was measured at 30 cm from Nalgene waste container containing all waste generated during the therapy. Calibrated survey meter RAM GAM 1 (Rotem Industries) was used for survey and RAM GENE 1 (Rotem Industries) was used for contamination monitoring. Post-procedure, hands of the Interventional Radiologists and angiographic sheath and entire area were monitored by contamination monitor. The percentage dose delivered was calculated by the following formula: %dose delivered = (IDr − RDr)× 100/IDr, where IDr = dose rate at 30 cm from the dose vials without lead; RDr = dose rate at 30 cm from the Nalgene waste container with radioactive waste.
Results: The average dose administered in our center was 2.33 ± 1.16 GBq per patient. The average dose rate at 30 cm from the unshielded dose vials 30 cm from the Nalgene waste container with radioactive waste was found to be 3.32 and 0.14 mR/h/GBq, respectively. The average post-therapy surface dose rate per GBq at anterior, right lateral, and left lateral abdomen wall was found to be 4.48, 6.29, and 1.34 mR/h/GBq, respectively. Dose rate at 1 m from the patient was found to be 0.2 mR/h/GBq. Average dose rate at 4 cm from outlet tubing just before termination of therapy was found to be 0.69 mR/h/GBq. Percentage of activity delivered per procedure was found to be 95.70%. No contamination was found on the hand of interventional radiologist so far. On two occasions, contamination of the angiographic sheathes ware was found, which was segregated as active west. Variation in the dose rate at different positions can be attributed to inter-individual variation in the lobe ablated, size, depth, and position of the hepatic lesson. However, the dose rate at 1-m distance was fairly estimated as 0.20 mR/h/GBq. Comparison of dose rate at 30 cm from vial and waste helped to assess the amount of actual dose delivery to patient as against the empirical value of 99% dose.
Conclusion: The 90Y-microsphere therapy is safe to perform from radiation safety aspect. The average dose rate at 1 m from patient is 0.20 mR/h/GBq, which is within permissible limit. The average dose administered is 95.7% of the dose estimated in the vial.
SPECT/CT and PET/CT in Imaging Neuroendocrine Tumors: Pearls and Patterns
S. Salam, C. Sit, F. U. Hassan, S. Navalkissoor, G. Gnanasegaran
Department of Nuclear Medicine Guy's and St Thomas' Hospital NHS Foundation Trust, King's College London, Royal Free Hospitxal, London, United Kingdom
Background: Neuroendocrine tumors (NETs) are relatively rare, slow growing, and have distinct clinical and biological characteristics. Radionuclide imaging and therapy play an important role in the management of NETs. Several radiolabeled SPECT and PET tracers are used in the diagnosis of NETs.
Purpose: (1) To review basic principles of radiolabeled imaging in NETs. (2) To review current literature on SPECT/CT and PET/CT imaging in NETs. (3) To illustrate lesion localization, characterization, and accurate diagnosis using SPECT/CT and PET/CT imaging.
Content Organization: (1) Illustrated review of the imaging appearances on SPECT/CT: (a) 111In-Octreotide, (b) 123I-MIBG, (c) 99mTc (V) DMSA, and (d) 111In-Octreotate (2) Illustrated review of the imaging appearances on PET/CT imaging: (a) 68Ga-DOTA, (b) 18F-FDG, and (c) 18F-DOPA. (3) Illustrated review of the concordant and discordant imaging appearances with SPECT tracers. (4) Illustrated review of the concordant and discordant imaging appearances (SPECT/CT vs. PET/CT imaging). (5) False positives and artifacts. (6) Miscellaneous. Summary-Major teaching points: Hybrid imaging is useful to localize, characterize lesion in patients with NETs. Hybrid imaging increases the diagnostic confidence and may be used as a one-stop imaging modality.
Fast Preparation of 131 I-MIBG for Therapy Purposes in Nuclear Medicine
Department of Nuclear Medicine, Agriculture and Medicine Research School, Karaj, Iran
Background: Meta-iodobenzylguanidine (MIBG) is an analog of the adrenergic neuron blocking guanethidine. This radiopharmaceutical is intensively used in nuclear medicine for both diagnostic imaging and targeted radiotherapy of neural crest derived tumors, such as neuroblastoma and pheochromocytoma.
Materials and Methods: A procedure based on Cu (I) assisted exchange radio-iodination was used for preparation of 131 I-MIBG. The method is based on the direct interaction of Cu+ with aryl-halide entity, leading to our complex formation. The procedure involved the addition of 1 mg of MIBG, 4 mg of tin sulfate, 5 mg ascorbic acid, and 30 ml of freshly prepared CuSO4, 5H2O (3.25 mg/ml), followed by 131 I-sodium iodide. All the reagents were pure. In a 10 ml reaction vial, 1 mg MIBG was added to 4 mg tin sulfate, ascorbic acid, and 5 ml water. Then, the vial was tightly closed and purged by N2 for 5 min. The mixture was heated at 120°C for 45 min in an oil bath. The final product was cooled and dissolved in 2 ml of 0.15 M sodium acetate solution prepared by using sterile N2-purged water for injection. The radiochemical yield and the purity were determined by thin layer chromatography.
Results: In this work, we succeeded in direct radiolabeling of MIBG by means of isotopic exchange. In the absence of oxygen, the complex was found to be stable for 24 h. Stability of the produced [ 131 I] MIBG was evaluated at different time intervals by checking the RC purity with paper chromatography. It was found that the labeling efficiency could be affected by several factors such as the composition of the reaction mixture, the temperature, and the period of reaction. The process produced high yields of radioiodination (>80%) with very high radiochemical purity (>98%) and high specific activity. pH of the complex was between 5 and 6. The results of biodistribution, as demonstrated in animal imaging studies, revealed physiologic distribution of the radiopharmaceutical and images were similar to those of the commercial product.
Conclusion: It is proven the above method fulfills the requirements for a simple and fast preparation of 131 I-MIBG for routine-production process. This method has received some acceptance because of the simplified set-up and fewer reagents required for the synthesis. The 131 I-labeled MIBG has high radiochemical purity and the deiodination is low.
Ga-68 DOTATATE PET/CT in Tumor-Induced Osteomalacia
A. l. A. Tamimi, D. Ng, S. C. Lim
Nuclear Medicine and PET, Singapore General Hospital, Singapore
Tumor-induced osteomalacia (TIO) is known as oncogenic osteomalacia. It is considered as a rare paraneoplastic syndrome manifested by increased levels of fibroblast growth factor 23 (FGF23) secreted by mesenchymal tumors, resulting in hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. The patients usually present with bone pains and multiple insufficiency fractures. The treatment of choice of TIO tumors is complete surgical resection of the tumor after localizing it; but this can be very challenging. As many TIO tumors can have somatostatin receptors, Ga-68 DOTATATE PET/CT scan is recently used as a tool to localize these tumors. We present a case of a 56-year-old Chinese lady with severe osteoporosis and multiple compression fractures of the lumbar spine. The patient gave a history of total hysterectomy with bilateral salpingo-oophrectomy (THBSO) 12 years ago for hydatid mole. She started traditional Chinese medicine (TCM) since then without hormone replacement therapy (HRT). Blood results showed hypocalcemia (normalized after IV calcium replacement) and hypophosphatemia (persistent after repeated cycles of IV phosphate replacement); dexamethasone suppression test was normal. On follow-up visits, the patient's phosphate level remained persistently low despite the phosphate supplements. The diagnosis of TIO was considered in the differential diagnosis. FGF23 was measured in the patient and showed high levels (422 pg/ml, most TIO reported >30 pg/ml), as well as 1,25-dihydroxy vitamin D levels were measured, which showed low levels (21.3 mg/L). The patient had no symptoms or signs that could help to localize the tumor; Ga-68 DOTATATE PET/CT scan was done for tumor localization which showed tracer avid sclerotic bone lesion in the left ischial tuberosity. Further, MRI scan showed corresponding lesion in the left ischial tuberosity, measuring 1.2 × 1.5 cm with low signal on T1 sequences and high signal on T2 sequences, and mild enhancement. The case highlights the promising role of Ga-68 DOTATATE PET/CT scan in localizing the TIO mesenchymal tumors in order to help in the management. Literature review of TIO and Ga-68 DOTATATE PET/CT scan was performed.
Safety and Efficacy of Peptide Receptor Radionuclide Therapy after Liver Transplantation in Progressive Neuroendocrine Neoplasms
H. Kulkarni, D. Kaemmerer, D. Hoersch, M. Hommann, R. Baum
Theranostics Center for Molecular Radiotherapy and Molecular, Zentralklinik Bad Berka, Germany
Aim: Patients with neuroendocrine neoplasms (NENs) can be offered the option of liver transplantation with the possibility of a complete cure, when metastases are limited to the liver. Peptide receptor radionuclide therapy (PRRNT) is a well-validated therapeutic modality for the management of metastatic NENs. The objective of this study was to assess the safety and efficacy of PRRNT after liver transplantation in progressive metastatic NENs.
Materials and Methods: This study included six NET patients (age 54 ± 9 years; 5 males and 1 female) who underwent liver transplantation (LTx). These patients developed extra-hepatic metastatic disease after LTx; only one patient had evidence of metastases to the transplanted liver. Intense somatostatin receptor expression in the metastases was confirmed on somatostatin receptor PET/CT (SSTR PET/CT) using Ga-68. All patients received PRRNT [4 cycles (n = 1), 3 cycles (n = 2), 2 cycles (n = 2), and 1 cycle (n = 1)] with Lu-177 DOTATOC or Lu-177 DOTATATE after LTx. The cumulative administered activity ranged from 6.9 to 29.3 GBq. PRRNT was performed under maximum nephroprotection. Blood cell counts, renal parameters (creatinine/BUN), liver function (liver transaminases, total protein, albumin, coagulation indices, etc.), and other laboratory tests (electrolytes, TSH, urine examination, and others) were assessed before therapy and serially during follow-up. In addition, renal function was evaluated by serial determination of tubular extraction rate (TER) using Tc-99m MAG3 (including dynamic scintigraphy) and of GFR using Tc-99m DTPA.
Results: None of the patients had grade 2 or higher hematological or renal toxicity or any deterioration in the hepatic function. Three patients had grade 1 erythrocytopenia and two patients had grade 1 renal toxicity, with a fall in TER of more than 20%. PRRNT resulted in partial remission in two, complete remission in one, and disease stabilization in two of the patients, while in one patient, the disease progressed.
Conclusion: These preliminary results show that PRRNT is safe, feasible, and an effective therapeutic option for NEN patients with progressive metastatic disease after liver transplantation.
Role of Ga-68 Somatostatin Receptor PET/CT in the Determination of Molecular Response to Radiofrequency Ablation of Hepatic Metastases from Neuroendocrine Neoplasms
H. Kulkarni, D. Kaemmerer, D. Hoersch, A. Petrovitch, M. Hommann, R. Baum
Theranostics Center for Molecular Radiotherapy and Molecular, Zentralklinik Bad Berka, Bad Berka, Germany
Aim: Radiofrequency ablation (RFA) is an important therapeutic option for the management of hepatic metastases, which are common in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). The objective of this study was to compare the molecular response to RFA in hepatic metastases of NENs as assessed by Ga-68 somatostatin receptor PET/CT (SSTR PET/CT), with response assessed by the morphological imaging modalities.
Materials and Methods: This study retrospectively analyzed 10 patients (mean age 53 ± 17 years; 6 males and 4 females) with known GEP-NENs who underwent RFA for hepatic metastases in a total of 17 liver segments. All patients had undergone SSTR PET/CT using Ga-68 DOTATOC as well as 4-phase CT, MRI, and ultrasonography (USG) before, and 3-6 months after RFA.
Results: Post-therapy 4-phase CT, MRI, USG, as well as SSTR PET/CT demonstrated complete necrosis of the metastases in 13 liver segments in 6 out of the 10 patients. In the remaining four patients, SSTR PET/CT demonstrated a minor molecular response in the metastases (>25% decrease in standardized uptake values on post-therapy PET). In two out of these four patients, there were no significant detectable changes on USG, while in one of the patients, CT and MRI could not detect any significant changes so to indicate response to RFA.
Conclusion: SSTR PET/CT is highly sensitive to evaluate therapeutic response to RFA, since it assesses the viability and molecular changes by accurate quantification of somatostatin receptor expression in the metastases. Our preliminary results demonstrate that molecular response assessment by SSTR PET/CT may be more accurate than determination of morphological changes for restaging of hepatic metastases of GEP-NENs after RFA.
Believe It or Not! Renal Function can Actually Improve After Peptide Receptor Radionuclide Therapy
H. Kulkarni, V. Prasad, R. Baum
Theranostics Center for Molecular Radiotherapy and Molecular, Zentralklinik Bad Berka, Bad Berka, Germany
Aim: Due to the possibility of renal damage in long term, administration of peptide receptor radionuclide therapy (PRRNT) in neuroendocrine neoplasms (NENs) concurrently needs adequate nephroprotection. We present the results in patients with metastasized progressive NENs treated with PRRNT, showing some sort of improvement in renal function after PRRNT.
Materials and Methods: Overall, more than 1000 patients with metastasized progressive NENs were treated with up to 8 cycles of PRRNT with a time gap of 3-4 months between successive cycles, using Y-90, Lu-177, or a combination of Y-90 and Lu-177 (administered sequentially, i.e., DUO PRRNT, or concomitantly, i.e., TANDEM PRRNT) labeled with DOTATATE or DOTATOC. PRRNT was performed under strict nephroprotection in all patients, i.e., with concurrent infusion of lysine/arginine (Rotterdam protocol). Patients treated with Y-90 were additionally co-infused with gelofusine. The changes in renal function were monitored in all the patients by serial measurements of serum creatinine and BUN, tubular extraction rate (TER) using Tc-99m MAG3, and by measuring GFR using Tc-99m DTPA. Long-term follow-up for at least 12 months was available in 668 patients. Thirty-seven patients who received five or more cycles of PRRNT have been followed up for more than 5 years.
Results: Overall, of 668 patients, 104 (15.5%) showed some sort of improvement in renal function after PRRNT, as determined by TER and/or GFR. Seven out of the 37 patients (18.9%) treated with five or more cycles of PRRNT and followed up for at least 5 years showed an improvement in TER after PRRNT.
Conclusion: Renal function can actually improve, when PRRNT is administered with appropriate fractionation, i.e. in relatively low doses with longer intervals between successive cycles and under adequate nephroprotection. This concept also minimizes the risk of development of chronic renal disease after PRRNT.
Evaluation and Calculation of Human Absorbed Dose of Tl-202(III)-DTPA-HIgG, Based on Biodistribution Data in Rats
A. Khorrami Moghaddam, A. Jalilian, V. Hayati, S. Shanesazzadeh
Department of Medical Physics, Tehran University of Medical Sciences, Teheran, Iran
Aim: We aimed to estimate the absorbed dose in normal organs and inflammatory tissue following intravenous administration of [201Tl](III)-DTPA-HIgG by using biodistribution data in inﬂammation-bearing rats.
Materials and Methods: The percentages of injected dose per gram of each organ were calculated. The Medical Internal Radiation Dose (MIRD) formulation was applied to calculate the absorbed dose for various organs.
Results: The inflamed tissue to blood activity concentration ratios were about 19 and 23.3 at 24 and 28 h post-injection, respectively. A 185-MBq injection of 201Tl-DTPA-HIgG into the human body might result in an estimated absorbed dose of 14.4 mGy for total body, and the highest absorbed dose was in the kidney with 1195 mGy and the second organ ws the spleen, followed by liver, the lungs, and adrenal which received 250.5 mGy, 58.64 mGy, 56.44 mGy, and 36.4 mGy, respectively.
Conclusion: Biodistribution of [201Tl](III)-DTPA-HIgG demonstrated significant inflammatory tissue uptake and low muscle and blood uptake, allowing for imaging of inflammatory tissues.
Assessment of Human Effective Absorbed Dose of 111In-DTPA-Buserelin Based on Biodistribution Rat Data
A. Lahooti, S. Shanehsazzadeh, A. R. Jalilian, M. B. Tavakoli
Department of Medical Physics and Biomedical Engineering, Teheran University of Medical Sciences, Teheran, Iran
Objective: In this study, we used a robust description of organ biodistribution owning to large amount of biodistribution data (source organs in dosimetry calculations); we tried to estimate the effective radiation absorbed dose into human organs following i.v. administration of 111In-labeled Buserelin by using biodistribution data in normal rats.
Materials and Methods: Rats were sacrificed at exact time intervals which were 0.25, 0.5, 1, 2, 4, and 24 h post-injections. The Medical Internal Radiation Dose (MIRD) formulation was applied to extrapolate from rat to human and to project the absorbed radiation dose for various organs in the human.
Results: Our estimation shows that for humans, if 185 MBq of 111In-DTPA-Buserelin were injected, it might result in an estimated absorbed dose of 24.27 mGy to the whole body. The highest effective absorbed dose was in kidneys with 28.392 mSv and the organs that received the next highest doses were spleen, bladder wall, uterus, adrenals, lungs, pancreas, liver, and ovaries which received 18.323 mSv, 16.130 mSv, 6.431 mSv, 5.626 mSv, 5.296 mSv, 5.224 mSv, 5.165 mSv, and 4.967 mSv, respectively.
Conclusion: Although this study followed by previous studies show good results for Gonadoreline receptors in the body, but due to high effective absorbed dose of 111In-DTPa-Buserelin, we suggest that using 67Ga-DTPA-Gonadoreline would have better results as a result of faster clearance of Gonadoreline and the absence of auger electron in 67Ga decay yields. Since the estimation of effective absorbed dose of 111In-DTPA-Buserelin in human shows it to be more than 15-folds higher than 67Ga-DTPA-Gonadorelin, it cannot be appropriate for diagnosis of GnRH receptor malignancies. In conclusion, this study is a good explanation of the importance of human absorbed dose estimations from rat data after getting promising results from the animals.
Biodistribution of Ultra Small Super Paramagnetic Iron Oxide Nanoparticles in Balb/c Mice
S. Shanehsazzadeh, M. A. Oghabian, F. Johari Daha, A. Lahooti, S. A. Haeri, M. A. Amanlou, B. J. Allen
Department of Medical Physics and Biomedical Engineering, Tehran, Iran
Background: Recently magnetic nanoparticles have been widely used for medical applications. One of their important applications is using these particles as MRI contrast agent. While various research works have been done about MR application of nanoparticles, there is not any research about USPIO uptakes in various organs. The aim of this study is to evaluate the biodistribution of Dextran-coated iron oxide nanoparticles labeled with 99mTc in various organs via intravenous injection in Balb/c mice.
Materials and Methods: Five mice were sacrificed at exact time intervals (1, 2.5, 5, 15, 30, and 60 min, and 2, 6, 18, 24, and 48 h post-injections) and the percentage of injected dose per gram of each organ was measured by direct counting from mice data from 19 harvested organs.
Results: The biodistribution of 99mTc-USPIO in Balb/c mice showed dramatic uptake in reticuloendothelial system (i.e., more than 75% of injected dose was in spleen and liver at 15 min post-injection). These nanoparticles still remain in liver till 24 h post-injection and their clearance is so fast in other organs.
Conclusion: These results suggest that it could be suitable to perform hyperthermia or to use nanoparticles labeled with beta emitter radioisotopes in order to treat spleen and liver malignancies.
Development of a Radiolabeled Glucagon for SPECT Imaging
J. Mahdokht, A. R. Jalilian, S. Moradkhani, F. Bolourinovin
Department of Chemical Pharmacy, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
67Ga-DTPA-GCG performances in vitro: Finally the radiolabeled compound was used for preliminary biodistribution studies in wild-type rats as well as glucagon binding assay in rat brain and SPECT Imaging.
Results: Absorption and biodistribution of radiolabeled glucagon in organs of rats were determined by measuring %ID/g at different times. The uptakes at 2 h post-injection were observed in organs such as liver, kidney, heart, fat, stomach, and uptake was less in pancreas, intestine, and spleen. SPECT images also demonstrated target-specific binding of the tracer at 4 h.
Conclusion: The results of the present study suggest that 67Ga-DTPA-GCG can be a suitable candidate for non-invasive imaging and biodistribution studies of GCG receptors in various physiological and malignant diseases with over-expressed GCGR.
Biological and Dosimetry Studies of Four Radiolabeled of Rituximab for Human Based on Distribution Data in Rats
E. Radfar, A. R. Jalilian, A. Bahrami-Samani, H. Yousefnia
Radiopharmaceutical Research and Development Laboratory (RRDL), Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran
Background: Radioimmunotherapy (RIT) is one of the most important and effective therapies for B-cell non-Hodgkin's lymphoma treatment. RIT is a targeted therapy combined from immunology and radiotherapy. Like the other common antibodies used against B-cell, rituximab binds with human B-lymphocyte-restricted differentiation antigen: CD20. Some beta emitters decay gamma photons whose energy levels are in the range of SPECT cameras. These gamma irradiations are feasible for imaging with treatment and use in diagnostic/therapeutic studies. The present article describes the preparation, biodistribution, and absorbed dose rate of 111In, 90Y, 177Lu, and 153Sm labeled anti-CD20 antibodies (rituximab) in human organs by acceptable approximations, after the injection to rats.
Materials and Methods: The macrocyclic bifunctional chelating agent, N-succinimidyl-1, 4, 7,10-tetraazacyclododecane-1, 4, 7,10-tetraacetic acid (DOTA-NHS), for conjugation to antibody was used to prepare DOTA-rituximab. The conjugates were purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated, and total concentration was determined by spectrophotometric method. Radiolabeling was performed at 40°C in 24 h. The final radiochemical purity of the radiolabeled monoclonal antibodies was checked by RTLC and HPLC as described earlier and in all cases was >95%. After the quality control studies, the final radioactive solution was injected intravenously into rats through their tail vein. The tissue uptakes of each injec tion were measured. Then we calculated S values for 177Lu and 153Sm by using specific absorbed fractions and data were used in manner analysis of radiolabeled and dosimetry for human. 177Lu-DOTA-rituximab, 111In-DOTA-rituximab, 90Y-DOTA-rituximab, and 153Sm-DOTA-rituximab were administered to normal rats separately (15 rats). The animals were killed at the exact time and the specific activities of different organs were measured by using an HPGe detector and a beta detector. It is necessary to calculate the %ID/g, since there are inherent limitations in measuring the activity of all tissues of each organ, such as bone and blood. The following equation was used to extrapolate biodistribution data of radiolabeled from rats to humans: %ID/g human organ = %ID/g animal organ × k (where k is the body mass animal/body mass human). This equation is obtained from the following equation with an algebraic formula: %ID human organ = %ID animal organ (organ mass human/body mass human)/(organ mass animal/body mass animal). There is a linear equation between ID and IA (injected activity), so %ID = %IA. The absorbed dose rate of each organ was calculated in the specific time by MIRD method with linear approximation in the measurement of activities.
Results: Absorption and biodistribution of radiolabeled compounds in the organs of rats were determined by measuring %ID/g at different times. The uptakes were observed in the limited organs such as the liver, spleen, and lungs, and barely in the kidneys, bone, and blood. Biodistribution of radiolabeled compounds was in agreement with other radiolabeled anti-CD20 antibodies species already reported. The dose rate estimation is based on more than 1.5 times of effective half-life of each radiolabeled compound.
Conclusions: The results showed that the high absorbed dose is in the liver, lungs, and spleen; and the absorbed dose of other organs (such as the red marrow and brain) is low as acceptable level values. Therefore, according to the kind of decay and energy, it is observed that Y-90 imposes the highest amount of absorbed dose to the body; the lungs (with 42% of the total dose) received a dose more than 8.5 mGy/MBq in 72 h. Due to the highest abundance of gamma photon decay, In-111 had the most fragments of organs that received dose; the liver and spleen received a dose of about 1 mGy/MBq (around 30% of total) in 72 h. For Sm-153 in 48 h, the highest absorbed dose was observed in the liver with 1.3 mGy/MBq (46%). Lu-177 had the least fragments of organs that received dose; the highest absorbed dose was observed in the spleen with 2.5 mGy/MBq (42%) in 168 h.
Investigating the Effectiveness of Low-dose and High-dose Radioiodine Ablation for Post-surgical Thyroid Remnants in Patients with Differentiated Thyroid Carcinoma at Kuala Lumpur Hospital
N. S. Ali, B. N. Lee, I. L. Shuaib
Department of Nuclear Medicine, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
Background: Many published literatures and guidelines support the use of low-dose radioiodine remnant ablation therapy for differentiated thyroid cancer, especially in low- and intermediate-risk patients. This is because there is equivalent efficacy demonstrated between high- and low-dose therapy. Kuala Lumpur Hospital has started low-dose remnant therapy with 30 mCi since 2006 in view of the increasing requests for radioiodine remnant ablation and limited inpatient facilities.
Objectives: To assess the effectiveness of low-dose compared to standard high-dose remnant ablation therapy. To determine the factors associated with successful ablation.
Materials and Methods: This is a cohort study of patients being administered with low-dose remnant ablation from Jan 2006 until June 2010. All patients selected were matched to patients receiving high dose according to their age group, gender, histopathology type, and tumor focality. Total of 64 patients were enrolled in the low-dose group and 69 in the high-dose group. As part of the preparation for the therapy and diagnostic whole body scan (WBS), all patients were required to undergo L-thyroxin withdrawal for 4 weeks and low iodine diet for 2 weeks. Remnant ablation was followed with diagnostic WBS at 6 and 12 months after therapy. Serum thyroglobulin and TSH were measured each time. Patient was considered in remission when there was no clinical evidence of disease, negative WBS, and thyroglobulin level was <10 mg/L. Non-remission was considered when there was either clinical evidence of disease, positive WBS irrespective of thyroglobulin levels, or negative WBS but with thyroglobulin levels ≥10 mg/L.
Results: Higher remission rate was observed in the high-dose group (54%) compared to the low-dose group (33%) (P < 0.05 at 95% CI). Other independent factors that were significant in determining remission were surgical margin involvement and lymphatic invasion in the Histopathological examination (HPE) (P < 0.05 at 95% CI). A multivariate analysis using multiple logistic regression showed that these factors predict remission by 23.6% (R2 = 0.236). The surgical margin involvement carried the highest risk of non-remission at 10 times risk, followed by lymphatic invasion at 6 times risk and low radioiodine dose at 2 times risky. Other factors considered in the study (patient's age, gender, race, type of surgery, type of HPE, tumor size, focality, and vascular invasion) showed no significant association with remission (P > 0.05).
Conclusion: High-dose radioiodine (80-100 mCi) remnant ablation is more effective than low-dose radioiodine (30 mCi) for remnant ablation in differentiated thyroid carcinoma. Surgical margin involvement, lymphatic invasion, and radioiodine dosage proved to be associated with highest risk of non-remission.
Evaluation and Dosimetry Studies of Human Absorbed Dose of Various Age Groups of 90Y-DOTA-Cetuximab Based on Distribution Data in Rats
A. Vakili, A. Jalilian, M. Ghazi-Zahedi, B. Salimi, D. Sardari
Medical Radiation Engineering, Islamic Azad University, Tehran, Iran
Background: Absorbed-dose calculations provide a scientific basis for evaluating the biologic effects associated with administered radiopharmaceuticals. In cancer therapy, radiation dosimetry supports treatment planning, dose-response analyses, predictions of therapy effectiveness, and completeness of patient medical records. In this study, we evaluated the organ radiation absorbed doses from intravenously administered 90Y-DOTA-Cetuxiamab and 90Y-DOTA-Rituximab for human in six age groups and both genders based on animal data.
Materials and Methods: After administration of two radiolabeled complexes to five groups of rats, they were sacrificed at exact time intervals (2, 24, 48, 72, and 96 h) and the percentage of injected dose per gram of each organ was calculated by direct counting from rat data. The Medical Internal Radiation Dose (MIRD) formulation was applied to extrapolate from rat to human and to project the absorbed radiation dose for various organs in a human. The mass correction factors were estimated based on MIRD/ICRP 60 recommendation for human in six age groups: Newborn, 1 year, 5 years, 10 years, 15 years, adult (25 years), and both genders. By using equations that MIRD suggests, radiation absorbed doses for all organs were calculated.
Statistical Analysis: All values were expressed as mean ± standard deviation (Mean ± SD) and the data were compared using Student's t-test. Statistical significance was defined as P < 0.05.
Results: The total body absorbed dose for all groups was >22 mGy due to pure beta emission of the applied radiopharmaceuticals. The effective dose resulting from an intravenously injected activity of 100 MBq was 56.7 mSv for a 60 kg female adult and 60.3 mSv for a 73 kg male adult. The highest absorbed dose for 90Y-Rituximab was in liver, lungs, and spleen; and absorbed dose of other organs was low as acceptable level value. The effective dose of 90Y-Cetuximab was 122 mGy for adult, 101 mGy for 15-year-olds, 109 mGy for 10-year-olds, 104 mGy for 5-year-olds, 133 mGy for 1-year-olds, and 143 mGy for newborn, and the organs that received the next highest doses were red marrow, bone, and also skin. The liver and kidneys had a high absorbed dose as excretory organs.
Development of Ho-166 Chitosan for Hepatocellular Carcinoma
H. Yousefnia, A. Jalilian, S. Zolghadri, M. Mazidi, A. Bahrami-Samani, M. Ghannadi-Maraghe
Nuclear Science and Technology Research Institute, Tehran, Iran
Background: Chitosan (CHITO) is a natural and biodegradable polysaccharide with wide range applications in bio-pharmaceutics, agriculture, and water treatment purposes, and an excellent molecule for treatment of hepatocellular carcinoma. In this research, 166Ho-CHITO complex production is described in detail, followed by determination of complex radiochemical purity, stability, and biodistribution (after intra-articular injection) in rabbits. Leakage of injected dose from injection site and its distribution in the rabbit organs was investigated using SPECT imaging up to 3 days.
Materials and Methods: Production of 166Ho was performed at the Tehran Research Reactor (TRR) using natHo (n, gamma) 166Ho nuclear reaction. 166Ho-holmium chitosan complex was prepared and Radiochemical purity was determined using ITLC. The stability of prepared 166Ho-holmium chitosan complex was checked up to 48 h after preparation. The distribution of injected dose in rabbit organs up to 72 h after transarterial injection of 166Ho-holmium chitosan complex solution was determined for control studies.
Results: Labeling yield increased with increasing chitosan concentration and reached above 98% when the concentration reached 35 mg/3 ml. The highest labeling yield was achieved at pH 2.8-3.2, while it decreased beyond this range. The labeling yield of 99% was achieved after 30 min. The effects of absence and presence of ascorbic acid (at various concentrations) as a complex stabilizer were also studied. Transarterial injection of [166Ho] holmium chitosan complex to rabbits showed that most of the injected dose had remained in liver 72 h after injection.
Conclusion: A kit formulation was developed for the in situ preparation of the radiopharmaceutical in remote clinical centers.
Development and Characterization of Clinical-grade 64Cu-DOTA-Trastuzumab for HER2/neu Oncology Imaging Using Dual-head SPECT
B. Alirezapour, A. R. Jallilian, M. J. Rasaee, S. Rajabifar, A. Sattari, M. R. Aboudzadeh, M. Pouladi, G. R. Aslani, P. Ashtari
AMIRS School, Nuclear Science and Technology Research Institute (NSTRI), Karaj, Iran
Background: Radiolabeled monoclonal antibodies as a tracer have shown great promise for cancer diagnosis and therapy. Trastuzumab (trade name; Herceptin) is a humanized IgG1 monoclonal antibody directed against the extracellular domain of the Human Epidermal Growth Factor Receptor 2(HER2). HER 2 receptor is overexpressed in 20-30% of the early-stage breast cancers, and these patients may be candidates for Herceptin treatment. 64Cu (b+ = 17%, b− = 39%, EC = 43%) is an important emerging biomedical radionuclide that is suitable for labeling a wide range of radiopharmaceuticals for PET imaging. Its intermediate half-life (12.7 h) permits PET evaluation of slow biochemical pathways, such as protein and peptide interactions with cellular targets, and distribution to satellite imaging and therapy centers. In the present study, copper-64 labeled Trastuzumab was prepared followed by the biodistribution studies performed in normal mice.
Materials and Methods: Herceptin as a monoclonal antibody against HER2 was conjugated with DOTA-NHS-ester (Macrocyclic), purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated, and total concentration was determined by spectrophotometrically. DOTA-Trastuzumab was labeled with 64Cu; then radiochemical purity, specific activity, integrity of protein after radiolabeling, immunoreactivity, and internalization study and cell cytotoxicity by SkBr3 cell line, and serum stability of 64Cu-DOTA-Trastuzumab were determined. The biodistribution studies were performed in normal rat and tumoral mice (breast carcinoma) (64Cu-DOTA-Trastuzumab i.v., 30 ± 5.5 mCi, 2 h, 6 h, 12 h, 18 h).
Results: The radioimmunoconjugate was prepared with a radiochemical purity of 96.1% (RTLC). The average chelate to antibody ratio (c/a) for the conjugate used in this study was 5.8:1. Conjugates were labeled with 64Cu at a specific activity of 5.3 mCi/mg. The final compound was stable in the presence of PBS at 37°C and room temperature. The sample showed to have similar patterns of migration in the gel electrophoresis. The accumulation of the radiolabeled antibody in lungs, liver, spleen, and other tissues demonstrated a similar pattern to the other radiolabeled anti-HER2 immunoconjugates. Conclusion: 64Cu-DOTA-Trastuzumab is a promising candidate for molecular imaging of PET for diagnosis and treatment studies and follow-up of HER2 expression in oncology.
In Vitro and In Vivo Evaluations of a Novel Potential Folate Receptor Imaging Agent
E. Mollarazi, A. R. Jalilian
Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
The aim of this study was to develop a new conjugate of folate (bis-cysteamide folate) labeled with technetium-99m as a new tumor-imaging agent. Folic acid was reacted with cysteamine after developing activated esters using N-hydroxysuccimide (NHS) and dicyclohexylcarbodiimide (DCC) at room temperature in two steps. After structure confirmation using conventional methods, the conjugated compound was labeled with 99mTc using two common labeling methods. The compound with >92% radiochemical purity was stable in final formulation and presence of human serum at 37°C at least for 6 h. Biodistribution study of 99mTc-bis-cysteamide-folate (99mTc-bCA-folate) in wild-type mice showed rapid clearance from the blood and excretion mainly through the renal/urinary pathway, with some elimination by way of the biliary route similar to other folate agents. In vitro experiments with MCF-7 and 4T1 as FR(+) (folate receptor positive) breast cancer cell lines after 60-min incubation with 99mTc-bCA-folate complex showed approximately greater uptake of radioactivity, significantly more than CHO cells (FR-negative). Some reduction of the internalization in the breast tumor was observed (blocked, compared to unblocked), which demonstrates the receptor specificity of this radiolabeled folate analog. Also, imaging study in cancerous balb/c mice by subcutaneous administration of 4T1 cells revealed high uptake of radiolabeled complex in tumor tissue after 3 h. Regarding its easy preparation, high tumor uptake, and simplicity of kit formulation, it seems that this radiolabeled complex can be used as a new radiopharmaceutical imaging agent in early diagnosis of tumor cells in tumor-bearing animal models.
Synthesis, Quality Control, Biological Evaluation by a Kinetic Model of [90Y]-DOTA-Cetuximab for Radioimmunotherapy Purpose
A. Vakili, A. Jalilian, K. Yavari, B. Salimi, D. Sardari
Medical Radiation Engineering, Islamic Azad University, Tehran, Iran
Background: Cetuximab (IMC-C225) is a monoclonal antibody directed against the epidermal growth factor receptor (EGFR) and its mutant isoform, EGFRvIII. The anti-epidermal growth factor receptor is clinically approved for the treatment of EGFR-expressing metastatic colorectal cancer and advanced head and neck cancer. Yttrium-90 is a useful radionuclide for radioimmunotherapy (RIT), due to its energetic beta emissions (Emax = 2.28 MeV), ready availability at moderate cost, and absence of g emissions, allowing outpatient RIT. Its half-life of 64 h is comparable to the uptake and residence time of many antibodies on the tumor. Biodistribution studies are expensive and difficult to carry out in humans, but such data can be obtained easily in rodents. The use of compartmental analysis allows the mathematical separation of tissues and organs to determine the concentration of activity in each fraction of interest. The overall goal of this study was to develop the radioimmunoconjugation of monoclonal anti-EGFR with 90Y as a potential tracer for RIT.
Materials and Methods: Cetuximab was successively labeled with [90Y] chloride (74 MBq) 2 mCi after conjugation with macrocyclics bifunctional chelating agent, 1, 4, 7, 10-tetraazacyclododecane-N, N, N, N-tetra-acetic acid mono-(N-hydroxysuccinimidyl) ester (DOTA-NHS), purified and concentrated by centrifugation using an Amicon Ultera-15 filter (Millipore, MWCo, 30000). Y-90 chloride was obtained by 90Sr/90Y generator. Radiolabeling was completed in 2 h by the addition of DOTA-Cetuximab conjugate at 42°C. The stability of radiolabeled compound was studied in human serum. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 96 h, and then a pharmacokinetic model was developed for therapeutic agent 90Y-Cetuximab to analyze the behavior of complex. We have developed a physiologically based pharmacokinetic model for scaling up data for mice to human. The mathematical model uses physiological parameters including organ volumes, blood flow rates, and vascular permeability; the compartments are connected anatomically.
Results: Radiochemical purity of 92% (using ITLC) was obtained for final radioimmunoconjugate (specific activity = 0.55 GBq/mg). The final isotonic 90Y-Cetuximab complex was checked by gel electrophoresis for protein integrity retention. Stability of radiolabeled protein in the presence of human serum was tested at 37°C for up to 24 h. Biodistribution studies demonstrated the highest ID/g% in the blood (2.89 ± 0.005 at 2 h) and the liver (2.19 ± 0.001). The temporal behavior of biodistribution of the complex is modeled and drawn as a function of time. Uptake of organs with EGFR expression such as blood and lung was maximum and increased post-injection of 90Y-Cetuximab for the first 48 h and then decreased.
Conclusion: This study demonstrated that 90Y-DOTA-Cetuximab is a potential compound for the treatment of EGFR-expressing cancers. The variation of pharmaceutical concentration in all organs is described with summation of eight exponential terms and it approximates our experimental data with precision better than 2%.
Development of a New In-111 Quinolate Complex as a Possible Imaging Agent
Y. Fazaeli, A. R. Jalilian, M. Aboudzadeh, S. Feizi
Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School, Karaj, Iran
Due to the interesting pharmacological properties of radiolabeled metal oxine derivatives, such as cell internalization, tumor avidity, and antiproteosome activity, ,[111In]-tris [8-hydroxy-2-methyl quinoline] ([111In]-HMQ) was developed in this work. [111In]-HMQ was prepared using [111In] InCl3 and 8-hydroxy-2-methylquinoline (HMQ) for 60 min at 100°C (radiochemical purity: >99% ITLC, >99% HPLC, specific activity: 13-14 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound (log P = 0.68). The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT up to 24 h. A detailed comparative pharmacokinetic study was performed for 111In cation and [111In]-HMQ up to 24 h. The complex is mostly washed out from the circulation through kidneys. A detailed comparative pharmacokinetic study performed for 111In cation and [111In]-HMQ was discussed. The SPECT images of the radiolabeled compound demonstrated high abdomen uptake 2-24 h post-injection, which is in agreement with biodistribution data. High biological stability of the complex compared to the other oxinates allows better accumulation time for imaging.
Development of In-111 and Ga-67 Maltolate Complexes as Imaging Agents
Y. Fazaeli, A. R. Jalilian, M. Amini, M. Aboudzadeh, S. Feizi, K. Yousefi, A. Rahiminezhad
Department of Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School, Karaj, Iran
Due to the antitumor activity of gallium maltolate complex, as well as recent findings on new targeted biomolecules in malignant cells by this complex, the development of radiolabeled gallium and indium complexes for future imaging studies was aimed at. [111In] and [67Ga] labeled 3-hydroxy-2-methyl-4H-pyran-4-onate (maltolate) were prepared using freshly prepared [111In] InCl3 and [67Ga] GaCl3 in 3-hydroxy-2-methyl-4H pyran-4-onate in a sodium salt form for 25 min at 45°C (radiochemical purity: >98% and >97% ITLC, >98% and >98% HPLC, specific activity: 15-17 GBq/mmol and 13-14 GBq/mmol), respectively. Stability of the complexes was checked in final formulation and human serum for 24 h. The partition coefficient was calculated for the compounds (log P = 0.56 and 0.40, respectively). The biodistribution of the labeled compounds in vital organs of wild-type rats was studied using scarification studies and SPECT imaging up to 24 h. The complexes are both mostly washed out from the circulation through kidneys, and furthermore, [67Ga]-maltolate could also be washed out from liver. These compounds can be an interesting tumor imaging agent due to the fact that the compounds have a potential therapeutic agent for cancer, infectious disease, and inflammatory disease.
Synthesis, Radiolabeling and Biological Evaluation of a New 111Indium-Porphyrin Complex as an Imaging Agent
Y. Fazaeli, M. Mirzaii, S. Sadeghi, M. Rahimi, S. Feizi, N. Piltan
Nuclear Medicine research group, Agricultural, Medical and Industrial Research School, Karaj, Iran
Porphyrins attract large attention because of their impersonation in the human body, ability to accumulate in many kinds of cancer cells, as well as magnetic and optical properties. Radiolabeled porphyrins have been developed for therapeutic purposes, such as 68Ga-porphyrins and 67Ga-porphyrins. In continuation of our previous work, [111In] labeled 5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin ([111In]-THPP) was prepared using freshly prepared [111In] InCl3 and 5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin (THPP) for 60 min at 800°C (radiochemical purity: >99% ITLC, >99% HPLC; specific activity: 13-14 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound (log P = 0.88). Biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT up to 24 h. A detailed comparative pharmacokinetic study was performed for 111In cation and [111In]-THPP up to 24 h. The complex is mostly washed out from the circulation through kidneys and liver. The SPECT images of the radiolabeled compound demonstrated high abdomen uptake 2-24 h post-injections, which is in agreement with biodistribution data. Higher water solubility of the complex due to strong hydrogen bonding of the complex is an advantage for rapid washout from the system leading to enhanced target: Non-target ratio of injected dosage of radio pharmaceutical.
Synthesis, Characterization, and Biological Evaluation of a New 131 Iodo Porphyrin Complex as an Imaging Agent
Y. Fazaeli, M. Mirzaii, N. Piltan, K. Yousefi, S. Feizi, G. Aslani
Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School, Karaj, Iran
Porphyrin derivatives have gained large attention due to their high tumor avidity, low toxicity, and rapid washout as potential radiopharmaceutical in radiolabeled form recently. In this work, we report labeling optimization of meso-tetrakis (pentafluorophenyl) porphyrin by 131 I to achieve [ 131 I]-TFPP. Biological evaluation of the prepared complex was studied in a fibrosarcoma tumor model to examine its potential as an imaging agent. [ 131 I]-TFPP was prepared via Meisenheimer complex intermediate, which strongly stabilized by an electron-withdrawing substituted group in ortho or para position for substitution. Such substitution activates the ring to nucleophilic substitution in para position of the phenyl groups and the ortho positions are no longer active due to high steric interference. The partition coefficient of the complex was calculated (log P = 1.98). The biodistribution of labeled compound in vital organs of normal wild-type rats and rats bearing fibrosarcoma tumor was investigated using scarification studies and SPECT up to 24 h. Biodistribution studies of 131 I-porphyrin demonstrated the high accumulation of radioactivity in the fibrosarcoma tumor.
Synthesis, Labeling Optimization, and Biological Evaluation of 111Indium 5, 10, 15, 20-tetrakis (3, 5-dihydroxyphenyl) Porphyrin Complex as an Imaging Agent
Y. Fazaeli, M. Mirzaii, S. Sadeghi, S. Feizi, A. Rahiminezhad, N. Piltan, K. Yousefi
Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School, Karaj, Iran
Due to the interesting pharmacological properties of porphyrins, the idea of developing a possible tumor imaging agent using SPECT by incorporating 111In into a suitable porphyrin ligand was investigated. In continuation of our previous work, [111In] labeled 5, 10, 15, 20-tetrakis (3, 5-dihydroxyphenyl) porphyrin ([111In]-TDHPP) was prepared using freshly prepared [111In] InCl3 and 5, 10, 15, 20-tetrakis (3, 5-dihydroxyphenyl) porphyrin (TDHPP) for 60 min at 800°C (radiochemical purity: >99% ITLC, >99% HPLC; specific activity: 13-14 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound (log P = 0.88). The biodistribution of the labeled compound in vital organs of wild-type rats was investigated using scarification studies and SPECT up to 24 h. A detailed comparative pharmacokinetic study was performed for 111In cation and [111In]-THPP up to 24 h. The complex is mostly washed out from the circulation through kidneys and liver. The SPECT images of the radiolabeled compound demonstrated high abdomen uptake 2-24 h post-injection, which is in agreement with biodistribution data. Higher water solubility of the complex due to strong hydrogen bonding of the complex is an advantage for rapid washout from the system leading to enhanced target: Non-target ratio of injected dosage of radio pharmaceutical.
Our Experience in the Safe Delivery and Internal Dosimetry Aspects of Radionuclide Therapy
Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore
Nuclear Medicine radionuclide therapy is rapidly developing as an additional treatment modality in oncology. Its unique characteristics are the systemic, yet selective delivery of radiation doses in target tissues, its non-invasiveness, the relative lack of immediate and late side effects, and the advantage that uptake and retention in the tumor can be pre-assessed by tracer studies. Many different tumor-seeking radiopharmaceuticals are being used for therapy by different routes and a variety of targeting mechanisms. Our current, safe method of delivery of radionuclide therapy is presented, as well as more general aspects and considerations, such as mechanisms for transport, storage, and the choice of shielding and radiation protection to staff in general are covered. The method of internal dosimetry for nuclear medicine radionuclide therapy will be presented as well.
Preparation and Quality Control of Lutetium-177 Bleomycin as a Possible Therapeutic Agent
H. Yousefnia, A. Jalilian, A. Bahrami-Samani, M. Ghannadi-Maragheh, F. Abbasi-davani, H. Afarideh
Nuclear Science and Technology Research Institute, Tehran, Iran
Due to the interesting therapeutic properties of 177Lu and antineoblastic antibiotic, bleomycin (BLM), 177Lu-bleomycin (177Lu-BLM) was developed as a possible therapeutic compound. Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of a natural Lu2O3 sample with a thermal neutron flux of 4 × 1013 n/cm 2 /s. The product was converted into chloride form, which was further used for labeling of BLM. In optimized conditions, a radiochemical purity of 98% was obtained for 177Lu-BLM shown by instant thin-layer chromatography (ITLC) (specific activity, 740 GBq/mmol). Biodistribution studies of Lu-177 chloride and 177Lu-BLM were performed in wild-type rats. The accumulation of the radiolabeled compound in lungs, liver, and spleen demonstrates a pattern similar to the other radiolabeled bleomycins. Lu-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models.
Development of [177Lu]-Tetraphenyl Porphyrin Complexes as Possible Imaging Agents
H. Yousefnia, A. Jalilian, A. Bahrami-Samani, M. Ghannadi-Maragheh, F. Abbasi-davani, H. Afarideh
Nuclear Science and Technology Research Institute, Tehran, Iran
Due to interesting therapeutic properties of 177Lu and tumor avidity of tetraphenyl porphyrins (TPPs), 177Lu-tetraphenyl porphyrin (177Lu-TPP) was developed as a possible therapeutic compound. Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 n/cm 2 /s. [177Lu] labeled tetraphenyl porphyrin ([177Lu]-TPP) was prepared using freshly prepared [177Lu]-LuCl3 and tetraphenyl porphyrin (TPPH2) for 30-60 min at 25°C (radiochemical purity: >97 ± 1% ITLC, >98 ± 0.5% HPLC; specific activity: 13-14 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 24 h. The partition coefficient was calculated for the compound (log P = 1.89). The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT imaging up to 24 h. A detailed comparative pharmacokinetic study was performed for 177Lu cation and [177Lu]-TPP. The complex is mostly washed out from the circulation through kidneys and can be an interesting tumor imaging/targeting agent due to low liver uptake and rapid excretion through the urinary tract.
Role of PET/CT in Initial Staging of Lung Cancer
X. C. Nguyen, D. K. Nguyen, V. K. Nguyen, M. T. Tran
PET/CT and Cyclotron, Cho Ray Hospital, HCMC, Vietnam
Background: PET/CT is an imaging technology that can provide metabolic activity from PET and anatomic information from CT in a single scan. PET/CT is extensively used in the world for diagnosis and follow-up of cancer, especially lung cancer. PET/CT was started in clinical practice from 2009 in Vietnam.
Aim: To assess the role of FDG-PET/CT application in initial staging of lung cancer, in comparison with conventional work-up (CWU).
Materials and Methods: Fifty-seven consecutive patients with lung cancer were enrolled prospectively to undergo FDG-PET/CT at Cho Ray Hospital from Dec 2010 to Dec 2011. There were 40 males and 17 females, with a mean age of 59 years (range: 40-84 years). There was an agreement between PET/CT with CWU on initial staging of the disease in 47/57 patients (82.5%) with a Kappa of 0.68 and on staging of loco-regional lymph nodes in 38/57 patients (66.7%) with a Kappa of 0.56. Ten of 25 patients (40%) without distant metastasis diagnosed by CWU were modified as more advanced stage of the disease on PET/CT. Seventeen of 32 patients (53%) with metastases diagnosed by CWU had more organs of metastases on PET/CT. The common metastatic sites included bone (22 cases, 59.5%), brain (12 cases, 32.4%), adrenal (8 cases, 21.6%), lung (7 cases, 18.9%), and liver (4 cases, 10.8%). Six of 12 patients (50%) with brain metastasis showed no glucose hypermetabolism in brain metastasis on PET, but it was detected by contrast-enhanced CT of PET/CT.
Conclusion: FDG-PET/CT may be helpful in the initial staging of lung cancer. Adding PET/CT imaging in CWU for lung staging may be considered.
Pleuro-peritoneal Communication Detected by Technetium 99m-tagged Macroaggregated Albumin Radionuclide Peritoneal Scintigraphy in a Chronic Kidney Disease Patient on Peritoneal Dialysis
C. Macaisa, K. M. Dela Cruz
Department of Nuclear Medicine, University of Santo Tomas Hospital, Manila, Philippines
End-stage renal disease (ESRD) is one of the leading causes of mortality in the Philippines. The rise of ESRD coincides with the increase in the number of patients with diabetes mellitus and hypertension in the past few decades. ESRD patients either undergo peritoneal dialysis or hemodialysis. Continuous Ambulatory Peritoneal Dialysis (CAPD) has found wide acceptance as an effective treatment option. CAPD is an alternative to hemodialysis for high-risk and elderly patients. However, CAPD patients are at a higher risk for developing hydrothorax and pleural effusion. Determining the site of origin of the fluid is necessary for planning the treatment when these complications are encountered. This case presents the value of peritoneal scintigraphy in evaluating pleuro-peritoneal communication in patients undergoing CAPD. The case presented is an 83-year-old female diagnosed with chronic kidney disease secondary to hypertensive nephrocalcinosis, and presented with sudden-onset dyspnea and tachypnea after her first peritoneal dialysis. She was referred for peritoneal scintigraphy to detect any possible pleuro-peritoneal leak. Peritoneal scintigraphy was performed after intravenous administration of 185 MBq of Tc-99m MAA in 1 L of peritoneal dialysis fluid. Beginning at the 5 th minute of the study, a faint blush of activity was seen arising from the upper portion of the right hemi-abdomen into the right hemi-thorax. The activity was noted to increase in intensity in the succeeding images, eventually outlining the silhouette of the right lung. Delayed images showed more intense activity in the posterior views of the right lung. No activity was seen in the left hemi-thorax throughout the entire duration of the study. This confirmed the suspected pleuro-peritoneal communication in the right hemi-thorax, most likely in the posterior portion. Discontinuation of CAPD is often advised when there is acute hydrothorax. However, in some cases like the one presented in this paper, CAPD can be continued after surgical correction of the peritoneal leak that was localized by the peritoneal scintigraphy. Peritoneal scintigraphy is a safe, non-invasive, and sensitive diagnostic procedure to demonstrate pleuro-peritoneal communication. It may play an important part in decision-making for patients on peritoneal dialysis with suspicion of pleuro-peritoneal leak.
Significant Impact of a Single-end 18F-FDG PET-CT Study as a Prognostic Indicator and Predictor of Outcome in Non-metastatic Squamous Cell Cancer in the Head and Neck
P. S. Choudhury, S. Rawat, A. K. Dewan, S. K. Gupta, S. A. Rao, V. Chauban, A. Pruthi
Department of Nuclear Medicine, Radiation Oncology, Surgical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India
Background: Diagnostic accuracy in detection and functional assessment of viable tumor defines further decision-making strategies to ensure a longer disease-free survival in head and neck malignancies.
Objectives: To evaluate 18F FDG as a metabolic marker to evaluate post-treatment tumor burden, guide management where indicated, and most importantly its role in prognostication to predict outcome.
Materials and Methods: Forty-nine patients diagnosed as squamous cell carcinoma (SCC) of head and neck, with no distant metastasis on conventional staging workup, and who underwent treatment during 2008-2010 were included. All patients underwent 18F FDG PET-CT study (Siemens Biograph) between 2.5 and 4 months after completion of treatment. Standard whole body and regional PET-CT acquisition protocol was followed. CT was used for attenuation correction and localization without IV contrast. Interpretation was done jointly by Nuclear Medicine Physician and Radiologist in an integrated reporting format. Focal abnormal areas of increased metabolic activity (non-physiological) with SUVmax >3.0 (normalized to body weight) in the areas of known primary, lymph nodes or other areas of interest were taken as positive for active disease. Relevant statistical analyses were performed along with Kaplan Meier survival analysis. End points were either minimum 12 months disease-free survival or disease progression.
Results: There were 44 males and 5 females (mean 54.38 years). Multimodality treatment regimes (predominantly concurrent chemo-radiation) as decided in tumor board were administered in different primary malignancies like tongue (27%), pyriform sinus (15%), buccal mucosa (17%), larynx (13%), and other areas including oro-hypopharynx, vallecula, and floor of mouth (28%). PET was normal in 33/49 (67%) of patients (Group I) and showed active disease in primary/neck lymph node or both in 16 (33%) patients (Group II). Twenty-eight patients in group I had longer disease-free interval as compared to early progression in five patients. In group II, the PET findings were correlated with cytology/biopsy. Eight (50%) had a longer disease-free interval (post neck dissection in seven directed by PET findings). Shorter time to progression was seen in rest of eight patients. The mean time to relapse for the PET-negative and PET-positive groups (log-rank test) was 30.2 months (95% CI 27.0-33.3) and 14.8 months (95% CI 9.3-20.3), respectively. The sensitivity and specificity of PET was found to be 75% and 96.5%, respectively, with a positive predictive value (PPV) and negative predictive value (NPV) of 93.8% and 84.9%, respectively. The positive likelihood ratio was 21.75 and the negative likelihood ratio was 0.26 with a disease prevalence rate of 40.8%. Kaplan Meier survival analysis showed significant difference between the two groups (P = 0.003).
Conclusion: Our results show that a post-treatment PET-CT study as a single modality is the most significant prognostic indicator and accurately predicts outcome in SCC of head and neck origin, thereby helping in selecting appropriate management strategies and developing individualized treatment regimes.
SPECT-CT for the Diagnosis of Primary Hyperparathyroidism
M. Garcheva, R. Kovachea, J. Vlahow, G. Ganchev
Clinical Center of Nuclear Medicine, Radiotherapy and Oncology, Medical University-Sofia, Sofia, Bulgaria
Background: The visualization of the parathyroid glands can cause problems, especially in cases with retrotracheal or ectopic localization, which is not a rare situation. Ultrasound examination, while being very useful in cases with normal localization of adenomas by hypodense nodules detection, is ineffective in the above-mentioned cases, and is with difficulties when multinodular goiter coexists. Preoperative localization in this situation is mandatory not only for minimization, but also for the whole success of operation. We aimed to use SPECT-CT for helping in the detection and localization of the hyperfunctioning parathyroid glands.
Materials and Methods: A combination of subtraction planar scintigraphy (with application of 37 MBq 99mTc-pertechnetate and 740 MBq 99mTc-tetrofosmin) and SPECT-CT was performed in 70 patients with proven primary hyperparathyroidism (level of parathyroid hormone 97-1207 pg/ml). In six patients, the examination was done in order to detect a recurrence after previous surgery for parathyroid adenoma. After subtraction, a SPECT-CT with low-dose CT component was done according to the residual focal uptake, in order to reduce the exposure. The neck, or eventually part of the thorax was scanned. Surgery was undertaken in 35 of the patients, and 8 others underwent ablation.
Results: An increased focal uptake was detected in 62 glands after subtraction. The fused SPECT-CT images demonstrated the morphologic substrate of the residual uptake and determined the extent of operation: Retrosternal (in 4 cases), mediastinal (in 1 case), or limited to the neck. The precise retrotracheal localization in seven cases was also important for the minimal morbidity and for the success of surgery. In operated patients, the SPECT-CT derived diagnosis and localization were confirmed. In addition, thyroid pathology that may need operation was detected in two patients: two thyroid nodules with high uptake of tetrofosmin, adenomas according to the postoperative histology. Among the patients with suspected recurrences, SPECT-CT was positive in three patients. In two of the operated patients, a parathyroid carcinoma was proved. They were followed up 1 year later, and recurrence of the disease was found in one of them. The SPECT-CT examination visualizes the structure, corresponding to the residual uptake. In cases with ectopic localization or postoperative examinations, it helps a lot in the differentiation of parathyroid adenomas from other structures, which can be responsible for focal uptake after subtraction: Local esophageal inflammation, retained vascular activity, thymic remnant. It is also important to improve the overall diagnostic confidence in cases when an ablation instead of operation is planned.
Conclusion: We can conclude that SPECT-CT is a necessity in the planning of treatment and in the post-procedure follow-up of primary hyperparathyroidism.
Variations of Gates' GFR Among Various Workstations
R. M. Goco
Department of Nuclear Medicine, St Luke's Medical Center, Quezon City, Philippines
Background: Glomerular Filtration Rate (GFR) is one of the commonly used modalities to assess renal function. This test is readily available using different workstations. However, Gates' GFR results vary from one workstation to another. The credibility of interpreting these tests may be questionable if results were dependent on which workstation was used. If results generated between two workstations significantly vary, one can be used to generate a higher result, while the other for a lower one, thus adding more subjectivity to the test.
Objective: This study aims to determine if variations among different workstations are statistically significant.
Materials and Methods: Patients were randomly selected from the April-May 2012 Gates' GFR database. Images were acquired by a Philips Forte gamma camera and processed three times each in four different workstations (G. E. Entegra, G. E. Xeleris, Philips JETStream, and Siemens Syngo). Data were encoded in Microsoft Excel. Quantitative variables were analyzed using ANOVA. F value was set at 0.05.
Results: The statistical data clearly show that there is no significant variation among the results generated by each workstation. The Fc of the test system (3.68 degrees of freedom) is 0.27, way lower than the F value at 0.05 level of significance, which is interpolated at 2.73.
Conclusion: There is no significant variation among the results generated by each workstation. The four workstations involved in the study can be used to process Gates' GFR.
Measurement of Non-uniformity in Gamma Cameras: Effects of Crystal Hydration
M. Dimcheva, S. Sergieva, A. Jovanovska
Department of Nuclear Medicine, Sofia Center LTD, Sofia, Bulgaria
Background: Uniformity test is the most common practice in the present gamma camera quality control procedures, suggested by National Electrical Manufacture Association (NEMA), International Atomic Energy Agency (IAEA), and International Electro-technical Commission (IEC). Uniformity is a measure of camera's response to uniform irradiation of the detector surface. The routine quality control (QC) test must be assessed daily and after each repair, it must be critically evaluated and any non-uniformity must be eliminated before patient testing to eliminate artifacts and false-positive or false-negative patient results. The intrinsic uniformity is the response of the system without a collimator to a uniform flux of radiation from a point source, to monitor the condition of the NaI crystal and electronics. Two different uniformity parameters shall be determined: Integral uniformity and differential uniformity. Integral uniformity is a measure of the maximum pixel count deviation in the central field of view (CFOV) or useful field of view (UFOV). Differential uniformity is a measure of the maximum deviation over a limited range designed to approximate the size of a photomultiplier tube. The purpose of this study was to compare uniformity analysis results with symmetric energy window, asymmetric energy window set low, and asymmetric energy window set high on the Siemens Symbia T2 SPECT-CT camera.
Materials and Methods: Integral and differential uniformity analysis was performed by placing a point source 99mTc in front of the detector with removed collimator to measure the effect of correction matrix, source-to-camera distance, a count rate, and activity volume on intrinsic uniformity. The integral uniformity represents the maximum pixel count rate change over the indicated field of view expressed as percent. The differential uniformity is the maximum change over a five-pixel distance in the X or Y direction, thereby representing the maximum rate of change of regional count rate. A 15% energy window set symmetrically over the 99mTc photopeak is equivalent to 140 ± 10% keV or a window spanning 126-154 keV.
Results: The results, received from Detector 1, gave the following uniformity parameter values. The integral uniformity for the CFOV was found to be between 3.52% and 3.54%. The differential uniformity for the CFOV was between 1.57% and 1.70%, while that of the UFOV was between 2.45% and 2.00%. The results, received from Detector 2, gave the following uniformity parameter values. The integral uniformity for the CFOV was found to be between 10.05% and 9.46%, while the integral uniformity for the UFOV was between 10.86% and 10.12%. The differential uniformity for the CFOV was between 7.09% and 7.72%, while that of the UFOV was between 7.07% and 7.76%. Both asymmetric energy window images for Detector 2 showed clearly multiple focal spots due to crystal hydration: Discrete hot spots in the asymmetric low window image and discrete cold spots in the asymmetric high window image. The above results are not seen yet on the symmetric window image. We had replaced Detector 2 in order to avoid spots to become visible in flood images obtained with the clinical energy window (due to a defect within the crystal itself).
Conclusions: The uniformity of a gamma camera is the most important parameter that expresses the quality of the camera's performance. Non-uniform areas in the field of view can result in misdiagnosed patients and low quality of clinical services. Thus, it is essential to perform regular checks to ensure optimal performance of the gamma camera. Gamma cameras require regular testing, responsible operation, and expert knowledge of its governing principles to make sure that its performance stays within clinically acceptable levels.
Correlation of Wall Motion Score and Left Ventricular Ejection Fraction by Gated SPECT Myocardial Perfusion Imaging
R. Hussain, A. K. Sarker, S. M. F. Begum
Department of Nuclear Cardiology, Institute of Nuclear Medicine and Ultrasound, Dhaka, Bangladesh
Background: Assessment of perfusion has been the principle indication of referral for gated SPECT myocardial perfusion imaging (GSMPI). The 4DMSPECT software in addition to perfusion data provides reproducible measurements of left ventricular (LV) volumes, ejection fraction (EF), and wall motions. Though there is limited documentation of independent clinical value of measurement of these absolute volumes, assessment of LVEF and wall motion abnormalities plays pivotal role in the management of coronary artery disease.
Objective: To observe the correlation of wall motion score (WMS) and LVEF measured by GSMPI in patients with known or suspected coronary artery disease.
Materials and Methods: Twenty-nine patients (26M, 3F) with the age ranging from 32 to 68 years, with a mean of 54.3 ± 8.4 years, undergoing GSMPI between February and May 2012 were studied. Treadmill exercise stress was done in 8 patients and pharmacological stress with dobutamine infusion was done in 21 patients. For treadmill exercise test, Bruce protocol was followed and 10 mCi 99mTc-sestamibi was given i.v. at peak exercise, and then exercise was continued for one more minute. Pharmacological stress with dobutamine was done following Mayo clinic protocol and 99mTc-sestamibi was given i.v. at peak heart rate and infusion was continued for one more minute. Patients' symptoms, blood pressure, and three-lead ECG were monitored continuously, along with wall motion response at baseline, low dose, and peak dose and recovery phases to detect echocardiographic evidence of viability in coronary territories. With a double-headed SPECT camera (Siemens E cam), post-stress SPECT acquisition with ECG gating was done 15-30 min after stress injection. Rest study using the same acquisition method was done 45-60 min after rest injection of 30 mCi tracer on the same day. MPI results were analyzed by 4DMSPECT v 3.1 software to obtain WMS and LVEF values at stress and rest from the gated perfusion data.
Results: MPI results revealed four normal scans. Among the patients having abnormal scans, seven had fixed defects, three had reversible defects, and mixed defect were found in 15 patients. LVEF and WMS showed strong negative correlation both at stress (r = −0.969, r = −0.968) and rest (r = −0.971, r = −0.966).
Conclusion: WMS and LVEF measured by GSMPI in patients with known or suspected coronary artery disease are inversely proportional. This should play a fundamental role in the management of coronary artery disease.
PET/CT and SPECT/CT in Imaging Prostate Cancer: Tracers, Advantages and Limitations
S. Salam, S. Lewitschnig, C. Sit, G. Gnanasegaran, S. Osmany 1
Department of Nuclear Medicine, Guys and St Thomas' Hospital NHS Trust, London, UK and 1 Radlink PET and Cardiac, Singapore
Background: The successful management of prostate cancer depends on early diagnosis/detection and staging. Conventional radiological and radionuclide techniques are often used in the diagnosis, staging, and evaluation of metastases (nodal, soft tissue, and bone), treatment, and follow-up. In recent years, there has been increasing interest in the use of several specific and non-specific SPECT and PET tracers (18F-FDG, 18F, C11 acetate, C11-choline, etc.) in the investigation of prostate cancer both primary and skeletal metastases. The current and evolving SPECT and PET tracers have several advantages and limitations.
Purpose: (1) To review basic principles and biodistribution of various SPECT and PET tracers in the investigation of primary and metastases. (2) To review current literature on the role of SPECT and PET tracers in imaging prostate cancer. (3) To review the potential clinical indications of SPECT and PET tracers in patients with prostate cancer.
Content Organization: (1) Illustrated review of the imaging appearances: Primary diagnosis, staging, recurrence, and management of cancer patients using various tracers. (2) Illustrated review of the SPECT/CT imaging appearances of bone metastases using SPECT tracers. (3) Illustrated review of the PET/CT imaging appearances of bone metastases using PET tracers. (4) False positives, artifacts. and limitations.
Summary: Major teaching points: (1) Radionuclide SPECT and PET tracers are useful in the investigation of prostate cancer, both for primary diagnosis and assessment of distant metastases and (2) development and validation of diagnostic algorithms for using SPECT and PET tracers may be useful for optimal and appropriate usage of these tracers.
Clinical Interest of Hybrid Imaging in Lung Cancer
B. R. Nozha, K. Rachid, A. Amina, G. Hasna, O. Rachid, G. Imad
Nuclear medicine, IBN Sina Hospita Chis IBN Sina, Rabat, Morocco
In Morocco, the most prevalent cancer is breast, followed by lung, cervix, colorectal, non-Hodgkin's lymphoma, and prostate and stomach cancer. Pediatric cancer is estimated at 1200 new cases per year (4%). Breast cancer is the most common in women (36.1%), followed by cervical cancer (12.83%). Lung cancer is the most common cancer in men (23.8%), followed by prostate cancer (8.3%). Cancer is considered nowadays as one major cause of death (7.2%) in Morocco and constitutes one major problem of public health. Morocco now has a National Plan for Cancer Prevention and Control (NCPCP). It is the outcome of an effective partnership between the Cancer Foundation and Ministry of Health. However, nuclear medicine and, particularly, hybrid imaging are actually the best relevant exams in the management of cancers. The information obtained from SPECT-CT and PET-CT changes the management of patient in oncology. Hybrid imaging can improve management of cancer in different fields. SPECT-CT is the first step to optimize theranostics in daily routine, such as management of bone lesions in patients with cancer, and PET-CT optimizes the management of patient care. At IBN Sina hospital, we do more than 50 bone scintigraphies per week for patients with cancers. SPECT-CT allows precise localization of equivocal lesions and their characterization as malignant or benign. SPECT-CT offers the unique opportunity to correlate the scintigraphic findings with anatomical images for better classification of indeterminate, non-diagnostic bone lesions detected at 99mTc-MDP scintigraphy in patients with extra-skeletal cancers. We will present some relevant cases of lung cancer and how hybrid imaging improves patient care. All in all, we have five PET-CT and three SPECT-CT; PET-CT is being incorporated increasingly in clinical protocols in oncology and national cancer management. Hybrid imaging is actually the best exam in nuclear medicine in the management of cancer and it will play a relevant role in diagnosis and therapy (theranostics).
The Clinical Impact of 18-F Flurocholine PET/CT in the Management of Prostate Cancer
A. Kannivelu, B. Magsombol, K. Loke, A. Goh, A. Tan
Nuclear Medicine and PET, Singapore General Hospital and Khoo Teck Puat Hospital, Singapore
Aim: The aim of the study is to determine whether 18-F fluorocholine PET/CT (FCH PET/CT) is useful in identifying local, nodal, and metastatic disease of prostatic carcinoma in correlation with clinical (biochemical and histological) diagnostic criteria, and also to compare FCH PET/CT with other imaging modality, Magnetic Resonance Imaging (MRI) pelvis in terms of detectability efficiency.
Materials and Methods: Between April 2010 and July 2011, 45 patients of our hospital were selected retrospectively who underwent FCH PET/CT study for evaluation of Ca prostate. Clinically they were considered positive patients when they had raising trend of PSA or histologically proven malignancy or both, and they were considered clinically negative when they did not have either. The FCH PET/CT findings were divided into three categories: (1) local disease: prostatic and extracapsular involvement; (2) nodal disease: pelvic and paraaortic nodes involvement; and (3) distal metastases: bones and lungs. FCH PET/CT and clinical results were compared and analyzed for correlation. Among the 45 patients, 17 patients also underwent MRI pelvis for disease surveillance. MRI pelvis findings were also divided into three categories as FCH PET/CT scans. Results of the two imaging modalities were compared in overall conclusion and in individual categories, and analyzed for accuracy with clinical parameters' correlation.
Results: In our study comprising 45 patients, 42 patients were clinically positive and 3 patients were clinically negative. In the clinically positive group (n = 42), 39 patients were FCH PET/CT positive and 3 patients were equivocal or negative. In the clinically negative group (n = 3), 2 patients were FCH PET/CT negative and 1 patient was equivocal. Thus, there is a good correlation between findings of FCH PET/CT and clinical parameters in 41 out 45 patients (about 91%). In the subgroup of 17 patients who underwent both FCH PET/CT and MRI pelvis, all the patients were clinically and FCH PET/CT positive. But MRI pelvis was positive in only 12 patients (negative in 4 patients, equivocal in 1 patient) with correlation of 70%. Comparing the FCH/PET and MRI, MRI had missed three local diseases and two nodal diseases that were diagnosed in FCH PET/CT, in contrast FCH PET/CT had missed one metastatic disease of bone that was diagnosed in MRI.
Conclusion: Our study demonstrated that the correlation between clinical diagnostic criteria and FCH PET/CT is good and FCH PET/CT can be used as an imaging tool for better disease localization. Even though FCH PET/CT detects more local and nodal disease in comparison to MRI, the MRI appears to have more value in diagnosing bone involvement due to its inherent sensitivity to image bone marrow. However, the small number of our study group limits the confidence level, which may warrant a future study with larger number of patients for determining our future diagnostic protocol.
The Role of Sentinel Node Biopsy in the Prediction of Metastatic Spread in Malignant Melanoma
A. M. Zamfirescu
Metabolic Radiotherapy, Bucharest Oncology Institute, Bucharest, Romania
Background: Malignant melanoma represents one of the most studied malignancies due to its highly increasing incidence and lack of efficacy of the known therapies in advanced stages. In early stages, the cure rate reaches 90%, but in locally advanced and metastatic settings, the median survival rates are 24 months and 6 months, respectively. The most important prognostic factors remain the thickness of invasion and the lymph node status. That is why, the importance of lymph node staging and of sentinel lymph node biopsy consequently increases constantly.
Purpose: In our study, we intend to estimate the role of sentinel lymph node biopsy in the prediction of metastatic spread. We try to find a correlation between the histological evaluation of the sentinel lymph node and the time of recurrence.
Materials and Methods: One hundred and two patients were included in the study between Jan 2007 and May 2012. The patients were referred to the Oncology Institute after resection of their primary melanoma. After surgery, all patients were staged using imaging methods (CT or MRI) and sentinel lymph node detection and biopsy. Patients with distant metastases were excluded. The patients received treatment according to their stage (no treatment for early stages, interferon for locally advanced stages, and chemotherapy +/- external beam therapy for metastatic stages). All the patients were followed up for recurrence using the same imaging methods as at baseline, every 3 months.
Results: The sites of the primary melanoma were as follows: Head and neck - 8 patients, trunk - 41 patients, upper limb - 13 patients, and lower limb - 40 patients. The histological tumor staging for the melanoma was between T1a and T4b, with Breslow indices between 0.25 mm and 20 mm and Clark indices between II and V. We have surgically explored 123 lymphatic basins. Sentinel lymph node was found positive in nine patients. The patients with ulcerated tumors received adjuvant interferon low dose. The patients with positive lymph node received adjuvant high-dose interferon. None of the patients with positive lymph node developed distant metastases at 3 years follow-up interval. Seven patients with pN0sn developed distant metastases at different time intervals after sentinel node biopsy.
Conclusions: Sentinel lymph node biopsy represents the best method for lymph node staging. The presence or absence of sentinel lymph node invasion represents one of the most important prognostic factors for metastatic spread in malignant melanoma. The lymph node staging has a major impact in adjuvant treatment selection.
Role of Contrast-enhanced 18F-FDG PET-CT in Restaging of Pancreatic Carcinoma
A. Gandhi, S. Simon, M. Indirani
Department of Nuclear Medicine and PET-CT, Apollo Hospitals, Chennai, India
Background: Contrast-enhanced CT (CECT) scan is the modality for restaging at present. However, CT is generally limited in its ability to resolve small peritoneal surface metastasis, small liver metastasis, and micro-metastasis to lymph nodes and distant metastases. We assess the utility of contrast-enhanced PET/CT in restaging of carcinoma pancreas over CECT.
Materials and Methods: Thirty-six patients who were suspected cases of recurrent pancreatic carcinoma, referred to radiology department for CECT abdomen and also underwent contrast-enhanced PET/CT scan. CECT was performed on Phillips 64 slices CT scanner by giving 100 cc i.v. contrast (Omnipaque 350) along with oral contrast to better delineate the gut. CECT was acquired at 120 kVp and 300 mA and slice thickness of 5 mm which was reconstructed into thinner slices up to 1.25 mm in standard reconstruction algorithm. PET/CECT was performed on Phillips Gemini TF PET-CT (64-slice) scanner by giving 100 cc i.v. contrast along with oral contrast. PET scan was performed using 1.5 min per bed position from head to mid-thigh region in 3D TF mode. Images were reconstructed in 5 mm slice thickness. CT of PET was acquired at 120 kVp and 300 mA and slice thickness of 5 mm, which was reconstructed into thinner slices of 1.25 mm in standard reconstruction algorithm. We also tried to find the correlation between a common tumor marker used for pancreatic tumors, CA 19-9, and FDG PET/CT imaging.
Results: Contrast-enhanced PET/CT scan found evidence of recurrent disease in 25 out of 36 (70%) patients, which is significantly higher as compared to 18 out of 36 patients (50%) of local and/or distant recurrent disease on CT alone. Out of 25 patients, 9 patients (35%) had local recurrence (retrospectively confirmed on CT); 2 of 4 patients had suspected mass lesion in CT which were not FDG avid so were considered as fibrotic changes on PET/CT images. Four patients had nodal diseases with or without local mass and the remaining 100 (40%) patients were having distant metastatic disease (lungs, liver, and skeletal lesions). Totally 16 out of 36 (45%) patients had raised CA 19-9 levels. Only 7 (44%) out of these 16 patients had positive CT findings on CT scans. When PET/CECT images of all 16 patients with high CA 19-9 were correlated, 14 (89%) had positive findings. But we found that only 11 out of total 25 (~43%) patients (PET/CT positive) had raised CA 19-9 levels. PET/CECT detected recurrent lesions in higher numbers of patients (70%) than those detected by CT (50%). This difference was more pronounced in the postoperative regions where ~36% of the patients with recurrent disease had lesions (only 15% in CT). FDG-PET/CT may be useful in patients with rising tumor markers and negative CT, to detect new systemic tumors, and assess the surgical bed for. A negative CA 19-9 level does not exclude the possibility of recurrent disease.
Conclusions: Contrast-enhanced 18F-FDG PET/CT is the modality of choice in the evaluation of the patients with recurrent pancreatic cancers. Raised tumor marker levels and normal anatomical scan form the strong indication for the evaluation with 18F-FDG PET/CT. CA 19-9 is a sensitive marker in evaluation of recurrent pancreatic carcinoma and shows good correlation with contrast-enhanced 18F-FDG PET/CT. However, it cannot predict the tumor activity within the body. A normal CA 19-9 value does not exclude the possibility of a recurrent disease and should be investigated if clinically warranted.
Controversy Over Dense Breast Imaging: Are We Using All the Armaments in Our Arsenal; A Review of Molecular Breast Imaging's Potential Role in the Battle Against Breast Cancer
Nuclear medicine and PET, SGH, Singapore
In recent years, the controversy over the accuracy of mammography as a screening tool in women with dense breasts has continued to attract attention in the media, patient advocacy groups, and the medical community. Worldwide breast cancer remains as the most common cancer in women and the numbers that form the subgroup with dense breast parenchyma are inevitably substantial. The importance of the medical fraternity understanding all the available diagnostic tools for further evaluation in equivocal or indeterminate cases cannot be understated. Traditionally, the adjuncts used for further evaluation have been anatomically based modalities such as ultrasound and MRI. The use of functionally based imaging of the breast is relatively new but has undergone rapid progress over the past few years, with some demonstrating results far superior to mammography. We review the current available nuclear-based imaging modalities, paying particular attention to molecular and breast-specific imaging.
Site-specific Radioiodination of HER2-targeting Affibody Molecules Using Iodophenetylmaleimide Decreases Renal Uptake of Radioactivity
J. Strand, P. Nordeman, H. Honarvar, M. Altai, M. Larhed, A. Orlova, V. Tolmachev
Uppsala University, Uppsala, Sweden
Aim: Radiolabeled affibody molecules, small (7 kDa) scaffold-based targeting proteins, have demonstrated a high potential for radionuclide molecular imaging. One challenge in the use of affibody molecules is a high reabsorption in kidneys. One approach to overcome this issue is based on the fact that internalization of affibody molecules by cancer cells is slow, and advantage of residualizing labels is minimal for tumor targeting. The internalization in the kidneys upon reabsorption is rapid, and non-residualizing properties of a label would facilitate excretion of radiocatabolites and reduce renal retention. Earlier, we have shown that the use of radioiodinated 3-iodo-((4-hydroxyphenyl)ethyl)maleimide (I-HPEM) as a prosthetic group for site-specific labeling of cysteine-containing affibody molecules provides high tumor uptake, but low radioactivity retention in kidneys. We have hypothesised that the use of 3-iodophenetylmaleimide (IPEM) would further reduce renal retention of radioactivity due to increased lipophilicity of radiocatabolites.
Materials and Methods : Radioiodination of N-[(tri-n-butylstannylphenetylamine) phenethyl]maleimido and coupling of 125 I-IPEM to pre-reduced anti-HER2 Z HER2:2395 affibody molecule was optimized, and stability of labeling was tested in vitro. Binding specificity and cellular processing of 125 I-IPEM-Z HER2:2395 and 125 I-IHPEM-Z HER2:2395 were compared in vitro using HER2-expressing SKOV-3 cells. Biodistribution of 125 I-IPEM-Z HER2:2395 and 125 I-IHPEM-Z HER2:2395 were compared in NMRI mice at 1, 4, and 24 h after injection.
Results: Radiochemical yield of 125 I-IPEM was 74 ± 2%. An overall yield of radioiodination of 125 I-IHPEM-Z HER2:2395 was 45 ± 3%. The label was stable in a set of in vitro tests. 125 I-IPEM-Z HER2: 2395 bound specifically to HER2-expressing cells. Cellular retention profile of 125 I-IPEM-Z HER2:2395 indicated more rapid excretion of radiocatabolites than 125 I-IHPEM-Z HER2:2395 . In vivo, the renal uptake of 125 I-IPEM-Z HER2:2395 (24 ± 2 and 5.7 ± 0.3% ID/g at 1 and 4 h, respectively) was significantly lower than uptake of 125 I-IHPEM-Z HER2:2395 (50 ± 8 and 12 ± 2% ID/g at 1 and 4 h, respectively). 125 I-IPEM-Z HER2:2395 had higher uptake in liver at 1 h pi (4.1 ± 0.7% ID/g compared to 2.6 ± 0.1% ID/g for 125 I-IHPEM-Z HER2:2395 ), but the difference disappeared by 4 h pi (1.4% ID/g for both conjugates). Radioactivity uptake in stomach and salivary gland (organs expressing Na/I symporter) was significantly lower for 125 I-IPEM-Z HER2:2395 .
Conclusion: The main hypothesis has been confirmed: The use of more lipophilic linker permits to reduce renal radioactivity retention for radioiodinated affibody molecules. This can be applied for labeling of affibody molecules with 123 I for SPECT, 124 I for PET, and 131 I for targeted radionuclide therapy. It might be also helpful for other researchers developing imaging agents based on scaffold proteins.
Is PET and PET/CT Useful in Pediatrics?
D. De Leon, E. A. Barrenechea
Department of Nuclear Medicine, St. Luke's Medical Center, Quezon City, Philippines
The value of PET in the evaluation of various disease states, particularly in oncology, has been well-documented. Compared with its widespread application in adults, clinical use of PET in pediatrics is limited. Concerns of radiation exposure to the child, as well as lack of studies evaluating the diagnostic benefit of PET/CT in children, are a contributing factor. This study was conducted to review the usefulness of PET and PET/CT in the evaluation of pediatric patients and to identify unique FDG physiologic distribution in the sample population. All pediatric patients referred for PET scan from March 2002 to September 2010 were included in the study. The indication for referral was predominantly oncology related (93.5%). Of the 85 patients included, PET/CT was able to detect new sites of metastases in 5 patients and help resolve equivocal CT findings in 12 patients. Of six patients presenting with seizures, PET successfully localized hypometabolic areas in the brain in all cases, as probable seizure foci. Physiologic distribution of F18-flurodeoxyglucose (FDG) was noted in the thymus, adenoids/tonsils, laryngeal area, and supraclavicular brown fat. PET/CT is useful in selective pediatric cases. Its value in effectively evaluating pediatric malignancies allows for early initiation of appropriate treatment and discourages unnecessary diagnostics and treatments for benign lesions. Physiologic uptake unique to children should be considered to avoid misinterpretations, reduce unnecessary treatments and follow-ups, as well as provide an overall improvement in patient care.
Developing a Nuclear Medicine Outreach Program: The Polokwane Experience
Department of Nuclear Medicine, Polokwane Provincial Hospital, University of Limpopo, Polokwane Campus, South Africa
The Nuclear Medicine Department provides facilities for the administration of radiopharmaceutical agents to patients and patient imaging for diagnostic purposes and for therapy. Our department is the only government Nuclear Medicine Department in Limpopo, a province, and is responsible for providing service to a population of over 6 million people as well as part of neighboring Mpumalanga Province, neighboring countries of Zimbabwe and Mozambique. The Limpopo province has five regional hospitals and over 32 district hospitals, most of them situated in a driving distance minimally approximating an hour from our center. The department provides a comprehensive and accessible service. Providing a 24-h service to the community, which includes being available to assist with any emergency scans, providing clinical guidance, and assistance with management and guidance toward further imaging required by the clinician. Currently, the department has been functioning with one single-head gamma camera. We are expecting an SPECT/CT camera. There were several difficulties being faced. The most severe was the lack of clinical understanding of the clinical importance of nuclear medicine by the medical personnel. To address, this we decided the best route would be educating the doctors and healthcare workers. The aim is to educate the clinicians on nuclear medicine techniques, available procedures, the feasibility of diagnostic and therapeutic tools, to encourage a good relationship with the surrounding hospitals and to assist and equip our clinicians toward global/overall clinical management and improve morbidity and mortality of our patients. We held presentations at the clinical meetings of the hospitals within the province, covering several topics which are relevant to the community: Thyroid, skeletal, infection imaging, ventilation and perfusion scintigraphy, renography, cardiovascular scintigraphy, cerebral perfusion imaging, brain death, etc. In addition, we created nuclear medicine brochures specifically directed at the clinicians. The main presentation was followed by a brief questionnaire/feedback form which was used to assist in making future presentations more specific to the clinical need of the region/district.
Tc-99m MIBI Scan in Multiple Myeloma
R. Mititelu, C. Mazilu, A. Rimbu, E. Danaila
Department of Nuclear Medicine, Central Military University Hospital, Bucharest, Romania
Background: In the past years many authors published a number of papers concerning the pattern of pathologic uptake of Tc-99m MIBI in patients with Multiple Myeloma. All authors reported a high sensitivity of MIBI scan in detection of bone marrow involvement especially in active stage of disease. Moreover, some authors suggested a prognostic significance of different patterns of uptake. Aim: To evaluate the efficacy of Tc-99m MIBI whole-body scan in diagnosis of Multiple Myeloma, in correlation with other imaging modalities, and mainly with MRI. Method: We performed a retrospective review of 29 cases of Multiple Myeloma patients, all of them in active stage of the disease. All of them underwent Tc-99m MIBI whole-body scan, MRI examination of the spine and a bone scan. We performed whole body MIBI scan in anterior and posterior projections, 10 - 20 min after iv injection of 740 MBq of Tc-99m MIBI, using a dual head gamma-camera Philips-Axis. We correlated results with X-ray, bone scan and spine MRI. Results: 86.75% of patients shown pathologic uptake of MIBI; 89.65% presented lesions in MRI scan of the spine. Bone scan detected lesions in 62.06% of patients. We noticed 3 patterns of pathologic uptake: focal increased uptake (9 patients), diffuse uptake (7) and mixed (8). 5/29 patients revealed a normal uptake of the radiotracer, probably due to over-expression of P glycoprotein. In these patients we found MRI pathologic changes (focal vertebral lesions on different levels). 2/29 patients had no pathologic changes on spine MRI; one of them has shown a pattern of diffuse uptake on the MIBI scan, and the other one has shown focal uptake of MIBI, but not in the spine (ribs and skull). Combined use of spine MRI and MIBI scans resulted in a sensitivity of 96.66% for detecting pathologic changes and the bone marrow involvement. Conclusion: 99mTc MIBI reflects the extent of bone marrow involvement and the activity of the disease. It has the advantage of whole body imaging in one single examination. Combined use of 99mTc-MIBI scan and spine MRI has a greater sensitivity than each method used separately (96.55% vs. 86.75% for MIBI and 89.65% for MRI).
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