|Year : 2013 | Volume
| Issue : 4 | Page : 222-230
Abstracts for Oral Presentation
|Date of Web Publication||18-Oct-2013|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Abstracts for Oral Presentation. World J Nucl Med 2013;12, Suppl S2:222-30
Development of a New [ 140 Nd]-porphyrin Complex as a Possible Tumor Imaging Agent
M. R. Aboudzadeh Rovais, Y. Fazaeli, M. Pouladi, F. Boluri, A. Sattari
Nuclear Medicine, Agricultural, Medical and Industrial Research School, Moazen Blvd., Karaj, Iran
Aim of the Study: Porphyrins are interesting because of their impersonation in the human body and ability to accumulate in many kinds of cancer cells, as well as magnetic and optical properties. In this work we report the synthesis of [ 140 Nd ] labeled 5,10,15,20-tetra phenyl porphyrin ([ 140 Nd]-TPP).
Materials and Methods: Total labeling and formulation of [ 140 Nd] Nd-TPP took about 30-60 min (RCP > 98% ITLC, >98% HPLC, specific activity: 13-14 GBq/mmol). The complex was stable in final formulation and human serum at least for 24 h. At the pH.7, the log P was 1.97. The biodistribution of the labeled compound in vital organs of Swiss mice bearing fibrosarcoma tumor was studied using organ counting in killed animals and PET imaging up to 4 h.
Results: The complex is mostly washed out from the circulation through liver and kidneys and can be an interesting tumor imaging/targeting agent due to high tumor uptake and rapid excretion through the urinary tract. The biological evaluation of the tracer evaluated in tumor-bearing animal models.
Conclusion: It is suggested that [ 140 Nd] Nd-TPP could be a possible PET tracer, however considering the good targeting of this compound in chest region, fast wash-out and the short half life neodymium-140, [ 140 Nd] Nd-TPP can be a suitable candidate for tumor imaging targeting applications.
Differentiated Thyroid Carcinoma in Young Patients Treated with I-131: Recurrent Disease and Outcome
J. Mihailovic, L. Stefanovic, K. Nikoletic, D. Srbovan, E. Matovina
Aim of the Study: To analyze recurrent differentiated thyroid carcinoma (DTC) in young patients treated with I-131.
Materials and Methods: In the period from January 1977 to December 2012, 1139 DTC patients were treated with I-131 in our institution.
Results: Among these patients, there were 52 (4.6%) patients younger than 20 years at the time of diagnosis. From this group of 52 pts, one patient was lost to follow-up and one patient had only a brief time of surveillance without confirmed clinical outcome. In total, we retrospectively analyzed 50 patients: 31 females, 19 males; mean age = 16.5 years, range = 7-20 years; median follow-up of 10 years (range, 1-30 years). Histologically, there were 3 follicular and 47 papillary carcinomas. Primary surgery was performed in several hospitals throughout the country using different surgical procedures without a uniform protocol. All patients were sent to our institution to receive radioactive iodine (RAI) since it was the only facility treating DTC with RAI until 2007. Thus, patients were divided into three groups according to the type of initial treatment: 1) total/near total thyroidectomy (TT/NTT) + RAI = 45 pts, combined with neck dissection (ND) and/or mediastinal dissection (MD) in 29 of them (ND = 21 pts; MD = 4 pts; ND + MD = 4 pts); 2) TT/NTT + ND = 2 pts; 3) partial thyroidectomy (subtotal thyroidectomy, lobectomy, tumorectomy)=3 pts. The probability of recurrence and its prognostic factors were calculated by the Kaplan-Meier method and differences were tested by Log-rank test.
Discussion: Recurrent tumor developed during the course of disease in 22.4%, with median time of 9 yrs (range, 1-23 yr). The probability of recurrences was 85.1 ± 5.2% after 5 years; 79.4 ± 6.2% after 10 years, and 62.9 ± 12% after 15, 20, and 23 years after the initial treatment. Recurrent disease was significantly influenced by the type of initial treatment, patients' age and patients' gender (P = 0.0001; P = 0.005; and P = 0.046, respectively). Histopathological type of the tumor, nodal and distal metastases at presentation had no influence on probability of recurrences (P = 0.998; P = 0.888; and P = 0.739, respectively). At the last check up, all patients were alive except for one patient who died from other causes, 48 (96%) pts achieved complete remission and 2 (4%) pts achieved partial remission.
Conclusion: DTC patients sometimes present with aggressive disease; recurrent disease is frequent, it generally has a good prognosis. Patients' age, gender, and type of initial treatment significantly influence the probability of recurrences. DTC in young patients require proper initial surgical treatment with additional radioiodine therapy. Since recurrence may appear at any time during the course of disease, these patients should have life-long follow-up.
Level of Thyroglobulin in Patients with Papillary Thyroid Carcinoma Received Radio Lodine Ablation Therapy
S. Frangos, L. Patsali, A. Vanezi
Nuclear Medicine, Bank of Cyprus Oncology Center, Acropoleos 32, Strovolos-Nicosia, Cyprus
Aim of the Study: According to the NCCN Practice Guidelines for papillary thyroid carcinoma (PTC), received radio lodine (RAI) ablation is not required for patients with classic PTC that have less than 1 cm and T1b/T2 (1-4 cm) N0 disease, particularly if the postoperative thyroglobulin (Tg) is <1 ng/ml, with the absence of interfering Anti-Tg antibodies. Anti-Tg concentration of <22 IU/mL is unlikely to cause clinically significant Tg assay interference. Patients come to our clinic after thyroidectomy by different surgeons. Postoperative Tg level can be an indication of how extensive the surgery was. Our scope was to find out how many patients in our department, who received RAI ablation therapy during the last 2 years, had Tg less than 1 ng/ml in the absence of interfering Anti-Tg.
Materials and Methods: A total of 234 patients received RAI therapy between January 2011 and December 2012 in our department. A total of 193 of them received RAI for ablation. A total of 171 of them had classic PTC. A total of 110 patients, age 20-78, had T1 or T2N0M0. All of them received 3,7 GBq Iodine-131 for ablation therapy according to our departmental protocol.
Results: A total of 38 out of 110 patients, had increased Anti-Tg (>22 mIU/ml) and were excluded from further evaluation. The value of Tg in the 72 remaining patients varied between <0.1 to 119.3 ng/ml. Eighteen patients had <1 ng/ml, 11 between 1 to 2 ng/ml, 20 between 2 to 9 ng/ml and 23 more than 10 ng/ml. Among the patients with Tg <1 ng/ml, 7 had increased anti-TPO antibodies, which could also interfere with the measurement of Tg. Among them, only three had both undetectable anti-Tg (<10) and undetectable anti-TPO (<5).
Conclusion: Out of 110 patients, only 18 satisfied the criteria of NCCN to have Tg < 1 ng/ml in the absence of anti-Tg. A total of 43 patients had Tg from 2 to 119.3 ng/ml. If the surgery is not performed in highly expert hands could lead to the need of ablation due to postoperative Tg level more than 1 ng/ml.
Lu177 Ethylenediamine Tetramethylene Phosphonic Acid for Pain Palliation in Patients with Skeletal Metastases
A. Shinto, K. Kamaleshwaran, Anandan, F. Rajan, P. Das, Thirumalaiswamy, Subash John, M. Nagarajan
Nuclear Medicine, KMCH, Avanashi Road, Coimbatore, India
Aim of the Study: To evaluate the effect of Lu-177 EDTMP (ethylenediamine tetramethylene phosphonic acid) in pain palliation and improvement in mobility and quality of life of patients with known disseminated skeletal metastasis.
Materials and Methods: The study consisted of a group of ten patients (Mean age = 61.3 years; 7 Male and 3 Females) with widespread bone metastasis - Ca Lung (4), Ca Prostate (3), Ca Breast (2) and Ca Oesophagus (1). Complete blood count (CBC) of each patient was taken at baseline and weekly after treatment for 6 weeks. Therapeutic dose of 3700 MBq (100 mCi) Lu177-EDTMP was then administered intravenously and images were acquired on a dual head gamma camera 1 day, 1 week, and 1 month post-therapy to determine tracer distribution. Pain palliation was recorded with the use of pain score (0-10), daily usage of analgesics and mobility score obtained on the day of therapy and 1 month after therapy. Karnofsky performance scores were also recorded prior to therapy and 1 month post-therapy.
Results: Significant reduction in the mean pain score was noted in all patients. Mean initial scores of 8-9 decreased to scores of 5-6 within 30 days of treatment. Four patients showed reduced or complete withdrawal of analgesics after a period of 4 weeks. Scans obtained at 1 month also showed a decrease in the uptake in the regions associated with pain relief. Mobility scores and mean Karnofsky performance scores of all patients, which was 55.3 initially showed a marked increase to 70.2. No significant blood related toxicity noted.
Conclusion: The results indicate that Lu177-EDTMP is an effective and safe therapeutic radiopharmaceutical for pain palliation of patients with disseminated skeletal disease.
Well-differentiated Thyroid Carcinoma of Childhood and Adolescence - A Long Term Experience at a Single Institute
F. Nasreen, N. Nahar, S. Sultana, Z. Jabin, F. Alam
Nuclear Medicine, Institute of Nuclear Medicine and Ultrasound, Shahbagh, Dhaka, Bangladesh
Aim of the Study: Thyroid carcinomas are rare in childhood and adolescence. The presentation is more advanced in case of children as compared to adults. However, the prognosis for survival in children is reportedly excellent. The aim of the study was to see the outcome of patients with well-differentiated thyroid carcinoma during childhood and adolescence treated at a single institute.
Materials and Methods : A retrospective study of 61 children and adolescent patient (age ≤18 years) with well-differentiated thyroid carcinoma (DTC) enrolled in the Institute of Nuclear Medicine and Ultrasound, Dhaka during the period of January 1986 up to December 2007 was carried out. To allow for a theoretical follow up of at least 5 years the last inclusion year was 2007 and follow up was carried on upto June 2013. All patients were treated by thyroidectomy followed by radioiodine therapy. Whole body scans, Tg, anti-Tg, and neck ultrasound findings were recorded 6 months to 1 year after initial therapy to classify patients into remission, persistent or recurrent disease. Status on last follow up was noted to estimate the survival rate.
Results: A total of 40 patients had papillary carcinoma, 18 had follicular variant of papillary carcinoma (FVPCT), and three had follicular carcinoma. Age range at diagnosis was 9 to 18 years with a mean of 15 ± 2 years. The number of patient ≤10 years was 5 and >10 years was 56. There were 12 males and 49 females giving a M: F ratio of about 1:4. Among the 61 patients 31 patients had lymph node metastases and one had both nodal and lung metastases at initial presentation. After 1 year follow up from the initial radioiodine therapy, 30 patients were in remission and 31 patients had persistent disease. Eventually, recurrence occurred in ten patients. Three patients died during the whole observation period and all of them were cancer related. One patient developed second carcinoma.
Conclusion: DTC in children and adolescent has a good prognosis in the presence of neck and distant metastases.
Five Year Experience of Strontium-90 Irradiation for Treatment of Post-operative Conjunctival Squamous Cell Carcinoma
R. Hussain, S. Sultana, K. S. A. Sultana, R. Perveen, K. K. Nath, F. A. Alam
National Institute of Nuclear Medicine and Allied Sciences, Bangabandhu Sheikh Mujib Medical University Campus, Shahbag, Dhaka, Bangladesh
Aim of the Study: 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: An analysis was done on 21 patients receiving post-operative beta irradiation from July 2008 to June 2013. There were 18 males and 3 females, age ranged from 30 to 85 years with a mean of 54.9 years. Study group includes 14 well differentiated, 1 well differentiated with invasion, 1 moderately differentiated with infiltration, 1 verrucous, and 4 carcinoma in situ SCC. All patients received 130 Gy (except one who received 60 Gy) to the post-operative sclera surface in five fractions by hand-held Sr-90 surface applicator. The patients were followed up at 1 week, 1 month, 6 month, and 1 year interval after beta irradiation.
Results: Out of the total 21 cases, 18 had follow-ups for more than 1 year. Two had recurrence within 1 year. Short-term complications included conjunctivitis, photophobia, watering of eyes etc., As for long term complications, two cases developed cataract. The short-term complications were self-limiting and had no serious effects. Two cases having cataract was over 60 years old, so it could not be clearly understood whether the normal ageing process or the radiation contributed more in the development of the cataract.
Conclusion: Sr-90 beta irradiation is effective and should be considered as a first-choice treatment option for post-operative conjunctival SCC.
Ga-68 DOTATATE: A Molecular Imaging Marker for Neuroblastoma
J. Shukla, R. Goel, R. Vatsa, P. Bhusari, D. Bansal, B. Mittal
Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigah, India
Aim of the Study: Neuroendocrine tumors (NET) are rare in children but are showing an increasing incidence. Neuroblastoma arises in the adrenal gland or in tissue in the nervous system that is related to the adrenal gland. The prognosis is related to the age (the younger, the better the prognosis), clinical stage and lymph node involvement at the time of diagnosis. Ga-68 DOTATATE PET-CT is a somatostatin analogue and is highly specific molecular imaging agent for neuroendocrine tumors. Our prospective study is focused on a Ga-68 DOTA-TATE PET/CT imaging in neuroblastoma patients.
Materials and Methods: Forty patients (n = 40) were included in the study. Ga-68 DOTATATE PET/CT was done on the same day when the patient was sent from the department of pediatrics as no prior patient preparation is required. The radiotracers were injected intravenously via cannula. PET/CT was performed 1 h post-injection. Pediatric patients were sedated orally after consulting with treating pediatrician. Intravenous sedative was given by pediatric residents only. Bone marrow biopsy and/or FNAC were also done. For Ga-68 DOTATATE was prepared in house using manual module and 68Ge/68Ga generator. The radiopharmaceutical was injected iv using cannula. 0.5-2.0 mCi of Ga-68 DOTATATE dosage were used for each patient. After a 60 min uptake period, the scanning was done with a dedicated PET/CT scanner present in the department having BGO detectors. The energy resolution at 511 KeV (%FWHM) is 10 with spatial resolution of 6 mm.
The diagnostic CT images were acquired using a matrix of 512 × 512 pixels, pixel size of about 1 mm and reconstructed using optimized parameters for attenuation correction. PET acquisition was taken for 3-5 minutes per bed position for two to five bed positions. PET data were acquired using matrix of 128 × 128 pixels with a slice thickness of 1.5 mm. Data obtained from CT acquisition were used for low noise attenuation correction of PET emission data and for fusion of attenuation corrected PET images with corresponding CT images. After completion of PET acquisition, the reconstructed attenuation corrected PET images, CT images, and fused images of matching pairs of PET and CT images were available for review in axial, coronal and sagittal planes, as well as in maximum intensity projections, three dimensional cine mode. After image reconstruction, a region of interest (ROI) was carefully drawn around the site of abnormal Ga-68 DOTA-TATE uptake on lesions in consequent 4-6 PET/CT slices. The SUV was calculated for quantitative measurement of activity of the lesion.
Results: The Ga-68 DOTATATE PET/CT findings were in accordance with bone marrow biopsy and FNAC. A total of 34 out of 36 patients were correctly staged on Ga-68 DOTATATE PET/CT scan. Ga-68 DOTATATE "PET/CT scan was negative in three patients. Out of two false negative patients, one was having poorly differentiated neuroblastoma. Another patient, due to faint uptake on Ga-68 DOTATATE, was given negative for neuroblastoma [Table 1]".
Therefore, in summary Ga-68 DOTATATE had a sensitivity of 91.89%, specificity 100.00% Negative. Likelihood ratio 0.08, disease prevalence 92.50%, and a positive predictive value of 100.00%. Ga-68 DOTATATE, in most of the cases, correlated well with disease status and histopathological findings. The assessment of treatment response was also accurate. With the use of PET/CT systems, better deﬁnition of Ga-68 DOTATATE abnormalities in bone and bone marrow is possible. PET/CT is also found useful in those patients, particularly in the neck region, where the resolution and co-registration of the Ga-68 DOTATATE scan with CT allows a better evaluation of the lesion and response to treatment. Ga-68 DOTATATE PET ﬁndings affected the therapeutic management in two cases of suspicion due to opsoclonus myoclonus. Ga-68 DOTATATE imaging also plays an important role in differential diagnosis of neuroblastoma due to overlapping symptoms of Wilms tumor and leukaemia and can detect higher lesion number in most of the patients. The relatively small patient cohort indicates that Ga-68 DOTATATE PET may be a useful imaging modality in providing particularly valuable information for pre-therapeutic staging of neuroblastoma. It is likely that Ga-68 DOTATATE PET may replace 131I-MIBG scanning in the management of neuroblastoma patients.
Conclusion: The availability of 68 Ge/ 68 Ga generator and easy Ga-68 DOTATATE synthesis, made Ga-68 DOTATATE imaging very convenient moreover, no patient preparation is required. It can be predicted that Ga-68 DOTATOC PET/CT may become a reliable, non-invasive tool for staging, restaging, differential diagnosis, and recurrence of neuroblastoma in patients. Ga-68 DOTATOC PET/CT may also help in selection of patients for therapy with radiolabeled somatostatin analogs like Lu-177 DOTATATE/NOC and Y-90 DOTATATE/NOC.
Development of New Potential Multiple Myeloma Theragnostic Agents
X. Camacho, M. F. Garcia, M. Fernández, N. Oddone, M. Moreno, J. P. Gambini, E. Riva, P. Cabral
Radiopharmacy, Nuclear Research Centre, Faculty of Sciences, University of the Republic, Montevideo, Uruguay
Aim of the Study: Multiple myeloma (MM) is a neoplasm of B lymphoid line that is characterized by clonal proliferation of malignant plasma cells in the bone marrow, producing monoclonal paraprotein (M) in blood and/or serum. Interleukin 6 (IL-6) is one of the key molecules related to growth, survival, and proliferation of MM cells. Tocilizumab is a humanized monoclonal antibody directed against the IL-6 receptor. The aim of this study was to radiolabel Tocilizumab with 99m Tc and 177 Lu to be used as a diagnostic and therapeutic (theragnostic) agent against MM.
Materials and Methods: Tocilizumab was derivatized with Suc-HYNIC and DOTA-NHS and MALDI TOF/TOF was used to determine the level of DOTA and HYNIC conjugation to Tocilizumab. This antibody was radiolabeled with 99m Tc using a mixture of Tricine/SnCl2.2H2O and 177 LuCl 3 . Radiochemical purity was determined by ITLC-SG and by HPLC. In vitro stability was studied in solution, serum, L-Cysteine, DTPA, and EDTA. In vitro binding and competition assays were performed with U266 and NCI-H929 MM cells lines upto 120 min and were analyzed by laser confocal microscopy. Biodistribution studies were performed in normal Balb/C mice at 1, 4, 24, and 48 h (n = 5). Results: HYNIC- and DOTA-Tocilizumab was efficiently labeled with 99m Tc and 177 LuCl 3 . The in vitro radiochemical stability studies of the radiolabelled antibody showed that the complexes formed were stable and no significant transchelation. In vitro binding and displacement assays confirm the specificity of recognition of 177 Lu-DOTA-Tocilizumab and 99m Tc-HYNIC-Tocilizumab by IL6R. After derivatization and labeling of the antibody, Tocilizumab retained its biological activity, being unaffected in its binding capacity to the surface antigen. Immunoreactivity of Tocilizumab to MM cells lines was determined by direct immunofluorescence. We observed a remarkable cell membrane staining of the MM cells. Nuclei were counterstained with DAPI. None of the control sections incubated only with buffer showed any degree of fluorescence. This data show that the humanized antibody Tocilizumab has affinity for MM. Biodistribution studies were performed to quantify localization and clearance of the radiolabeled antibody complex in normal tissues. Significant accumulation of radioactivity was found in liver, indicating that the primary route of clearance was through the liver. There was no other major uptake found in the organs at the observed time points.
Conclusion: 99m Tc-HYNIC-Tocilizumab and 177 Lu-DOTA-Tocilizumab were easily and rapidly labeled, with radiochemical purities greater than 90%. Our results suggest that these radiolabeled compounds could have a potential theragnostic role in the treatment of MM.
Customization of 90 Y- SIR Sphere Delivery Set: Technical Modifications in Our Institution Leading to Improved Radiation Safety and Logistics
A. K. Jha, A. Gandhi, S. Shah, A. Agrawal, N. Purandare, V. Rangarajan
Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India
Aim of the Study: Trans arterial radio embolization (TARE) is preferred over trans arterial chemo embolization (TACE) and other conventional ablation technique like radio frequency ablation (RFA) in various hepatic neoplasms with bilobar multiple and larger lesions. SIR-Spheres (Sirtex Medical) and Thera-Sphere (MDS Nordion) are the two FDA (USA) approved commercially available products. SIR-Spheres, the resin microspheres are polymer beads designed to be between 20 and 60 nm in diameter and loaded with 90 Y at a specific activity of 40-70 Bq per sphere. The dose provided by Sirex Medical is fixed 3 GBq and hence needs individualized dispensing in the hospital radiopharmacy. The method of dose dispensing and delivery of SIR-spheres were found to be unsuitable to the clinicians and hence we tried to customize as per suggestions by our team. Modifications were done to maintain sterility, reduce radiation exposure to personnel, and unhindered flow of particles into the catheter.
Materials and Methods: The SIR sphere dose preparation and dispensing is done in the radiopharmacy of nuclear medicine prior to shifting to Intervention Radiology for administration. Modification to maintain sterility: A standard calibrated CRC - 15BETA CAPINTEC INC dose calibrator is used for dose calibration. Sirtex Medicals provides Perspex syringe and delivery vial shield and Perspex delivery box. As per the company recommendation repeated agitation of the content is advised before drawing the dose from shipment vial and a 26 G needle is used as vent to release the pressure from the vials. The recommended isotope volume in delivery vial is 3 ml which is constituted using water for injection. The small sized 26G needle could induce pyrogens and microbes from the environment and hence we replaced it with a butterfly needle connected to a Millipore filter.
Results: This modification is able to maintain sterility and a pyrogenicity of the SIR sphere to prevent any kind of pyrogenic reaction or infection. Additionally, this prevented spillage through vent needle during dilution of the content in delivery vial or during agitation in shipment dose vial. Modification to reduce radiation exposure of personnel: The entire process of dose administration of SIR Sphere requires approximately 1.5-2 h. Though perspex shielding is provided with the delivery set, it is unable to stop bremsstrahlung radiation. So we have used a 13 mm lead glass shield to protect the professional from bremsstrahlung radiation during infusion. Modification for unhindered delivery of spheres: The spheres flow horizontally through the connector of the delivery tubes and the catheter tubing placed into the patient. A significant amount of spheres adhere to this site. By attaching an arm to hold the catheter vertically allows the sphere to flow smoothly in the direction of gravitational force and reduces the hindrance of the sphere to the junction.
Conclusion: By implementing the above described modification we are able to ensure the sterility and a pyrogenicity of the SIR Sphere. By using lead glass shield we are able to reduce the radiation exposure rate significantly.
Prospective Study of Skeletal Related Events Incidence in Patients Whom Radionuclide Therapy was Added for Bone Metastases and Primary Tumor's Treatment
N. Rasulova, D. Arybzhanov, Sh. Sagdullaev, V. Lyubshin
Nuclear Medicine, Republic Specialized Center of Surgery, Tashkent, Uzbekistan
Aim of the Study: Patients with metastatic cancer involving bone are also at increased risk of fractures, spinal cord compression, hypercalcemia, and immobility resulting in substantial medical-associated morbidities. It was reported that skeletal-related events (SREs) during the first year after the primary diagnosis of bone metastases can occurred in 41-71% of cancer patients. Moreover, 46.4% patients developed an SRE during a median follow-up time of 8.4 months. Bisphosphonates administration may reduce this risk to 17%. However, it has not been investigated if radionuclide therapy may influence the incidence of SREs. The aim of this study is to estimate the incidence of SREs in patients who received a complex therapy including radionuclide therapy by Sm-153 oxabifore by follow up over a period of 0-5 years after radionuclide therapy.
Materials and Methods: A total of 255 patients (191 female and 64 male, aged 26-82, mean age 55.8 + 10.8) with multiple skeletal metastases from prostatic carcinoma (51), breast carcinoma (162), lung carcinoma (12), kidney cancer (20), and other tumors (10) were studied. A total of 11 patients with impending cord compression prior to radionuclide treatment underwent vertebroplasty, 5 with vertebra fracture but without cord compression received radiotherapy. All patients were on the treatment of primary tumor and due to bone metastases were receiving bisphosphonates and Sm-153 oxabifore administration in standard dose of 37 MBq/kg body weight. Patients were followed up 0-5 years after radionuclide therapy.
Results: Within 5-40 months (mean period 17.7 + 9.8 months) 71 out of 255 patients (28.7%) died due to brain, lung, or liver metastases. A total of 6 out of 255 patients (2.3% cases) had SREs within 6-21 months (mean period 14.1 + 4.8 months) after Sm-153 oxabifore administration. Among six patients (four with breast cancer and two with prostate cancer), five were receiving radiotherapy due to previous vertebral fractures. No one who underwent vertebroplasty had a SRE later.
Conclusion: According to our data patients who received radionuclide therapy together with complex treatment which included bisphosphonates and treatment of primary tumors had a low incidence of SREs. It is possible that radionuclide therapy may help to prevent the incidence of SREs, although a study of a larger population is needed.
Cost-effective Custom Made P-32 Incorporated Alginate Gel Patches for the Treatment of Basal Cell Carcinoma
J. Shukla, V. Chaudhary, P. Bhusari, A. Reddy, D. De, B. R. Mittal
Departments of Nuclear Medicine and Dermatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Aim of the Study: Basal cell carcinoma (BCC) is the most common skin cancer and originates from the lowest layer of epidermis. Surgery and radiotherapy are the preferred treatment methods. However, in some cases surgery or radiotherapy may not be feasible. External radionuclide-based radiation therapy with the help of custom made locally applied radioactive patch is a useful way to treat superficial skin cancers. β-radiation has high linear energy transfer (LET) and low tissue penetration. We evaluated the utility of P-32 alginate gel patches in treating a case of BCC. The patches of alginate gel were standardized as an inert solid matrix to immobilize radioactivity. Tc-99m pertechnetate was used to study the distribution of radioactivity in the patch.
Materials and Methods: Sodium alginate solutions (4%) was spread on parafilm and dipped into anhydrous CaCl2 (0.2 M) solution for 30 min. The patches were washed with water and left for few hours for air drying. Radioactive solution ( 99m Tc and 32 P) was spread on the gel to uniformly distribute the radioactivity on pre marked 1cm 2 area and was left undisturbed to allow drying and avoid alteration in distribution. The images of Tc-99m incorporated patches were acquired under gamma-camera, ROIs were drawn and counts were recorded to study radioactivity distribution using different patterns. Patches were observed for 10 days to study integrity of the gel layer. P-32 incorporate patches were prepared in the same way. A teflon sheet of size bigger than the patch (~2 cm) was placed over the outer surface over the parafilm. The exposure rate was observed on outer and inner surfaces and also with and without teflon sheet. A patient with histopathologically proven basal cell carcinoma was recruited after obtaining ethical clearance from the Institutional Ethics Committee. Informed consent was obtained from the patient. The patient had a healed ulcerative lesion with indurated edge on the dorsum of the nose on left side with extension till the medial canthus of left eye. He was complaining of pain in and around lesion, perilesional itching, difficulty in opening the eye and serous discharge. Complete blood count and other relevant baseline investigations of the patient were performed before therapy. A clinical photograph of the lesion was taken; and size of the lesion was assessed with a thread based measurement. A customized patch 2 cm larger than the size of the lesion containing 1 mCi/per cm 2 P-32 was prepared and laminated to prevent direct contact of P-32 with skin and applied on the lesion. A teflon sheet of similar shape and 2 cm bigger in size was kept over the patch and the patch was fixed with adhesive tape. The patient was followed up on 4 th and 7 th days after the first sitting with the same patch applied on the facial lesion. Clinical assessment, photographic recording, and hematologic monitoring were done during the follow ups.
Results: The alginate gel layer was consistent and homogeneously distributed over parafilm. 99m TcO 4 - was used to study the distribution pattern of radioactivity on alginate film as P-32 has only beta emission and the patch containing P-32 cannot be imaged. The counts registered were almost similar which indicated the uniform distribution of the activity over the patches. P-32 patch was prepared with alginate gel using parafilm as a base. Radioactivity (P-32) was uniformly adsorbed on the gel layer. Exposure rate above the parafilm surface and on open surface was almost similar but was reduced by covering the patch with teflon sheet. Minor fresh ulceration was observed within the lesion after initial sitting of patch application and was managed by dermatologist with local applicants. On subjective scoring, more than 20% relief of clinical symptoms was experienced by the patient after first application. Pain subsided and eye lid movement were comfortable. After 2 nd and 3 rd applications and follow ups significant symptomatic relief was observed. On physical examination, the thick dark edge of lesion disappeared and the lesion showed signs of healing. Clinical photographs were taken before and after patch application. Visual and symptomatic improvement was observed on follow-ups. No haematological changes were observed. Alginate is a biocompatible polymer. Radioactivity was homogenously distributed on alginate gel. P-32 patch are custom made and can be placed over the patient's skin to treat the lesions by direct radiation, can be stored and reapplied according to treatment protocol. Preparation of patch is simple; application is painless and cost effective. Beta energy (max) of 1.71 MeV is suitable to be used in skin patch. Beta radiation delivers uniform radiation dose to the tumor but delivers minimum dose to the underlying surrounding and the adjacent tissue due to low tissue penetration (2-3 mm) therefore overcomes the disadvantages of radiotherapy. Teflon sheet was used to prevent irradiation to the normal areas.
Conclusion: Alginate gel patch can be stable and suitable alternatives for radionuclide patch preparation for superficial skin cancers. Also our single patient observation demonstrated that P-32 patch therapy can be simple, non-invasive, and safe out-patient therapeutic procedure in treating patients of BCC.
188 Re-zoledronic Acid: First-in-man Study
T. Kochetova, M. Smolyarchuk, V. Krylov, L. Voloznev, A. Lunev, V. Petriev
Department of Radiopharmaceutical Therapy, Medical Radiological Research Center, Obninsk, Russia
Aim of the Study: Zoledronic acid (ZA) is extensively used for palliation therapy in cancer patients with bone metastases due to its' high affinity to bone tissue. At the other side radionuclide therapy with bone seeking radiopharmaceuticals is used for the same purposes in patients with painful bone metastasis. A new radiopharmaceutical which combines affinity of ZA and efficiency of nuclear therapy is created. 188 Re was used to label ZA because of its' high beta-particles energy (up to 2.1 Mev), radiochemistry similar to 99m Tc and it is a generator-produced isotope. The aim of this study is to evaluate biodistribution, pharmacokinetic characteristics, safety, toxicity, and preliminary clinical effects of 188 Re-zoledronic acid.
Materials and Methods: First in the world three patients with painful bone metastases from prostate and breast cancer underwent palliative radionuclide therapy with 188 Re-zoledronic acid. All clinical investigation and laboratory test were performed. Also whole body bone scan with Rezoscan ( 99m Tc-zoledronic acid, ZAO Pharm-Sintez), which was performed in 1, 4, 20, 28 h after injection to evaluate the` pharmacokinetic and compare to 188 Re-zoledronic acid, were done before the treatment. All patients had metastatic lesions with high uptake of Rezoscan (>200% comparing to normal bone). 188 Re-zoledronic acid was synthesized in Radionuclide Therapy Department of MRRC using 188 Re eluated from sorption generator (GREN-1, Obninsk, Russia) and liophylisate from ZAO Pharm-Sintez. Radiochemical purity assessment was performed for each administration dose using thin-layer chromatography. The purity coefficient equalled more than 90%. Radiopharmaceutical was injected with the dosage equalled 16.5 ml of saline intravenously using syringe pump in 15 min. In 1, 4, 20, and 28 h after injections whole body bone scan was performed to assess biodistribution and pharmacokinetics. Excretion was assessed by urine radiometry. Safety was assessed by the patient's general condition, physical data, and laboratory analysis of blood. Preliminary evaluation of the effectiveness was assessed by changes of pain syndrome and the abolition of analgesic drugs. Follow-up data are in process of collection.
Results: All patients showed high uptake of 188 Re-zoledronic acid in metastatic lesions on scintigraphy. In 1 h p/a accumulation of the drug in bone metastases, in area of injection, blood and organs of the urinary system was observed. In the resulting scans, there is preferential accumulation in the metastatic foci and elimination through the urinary system. After 20 h p/a all patients showed moderate accumulation in thyroid and gastric mucosa which is typical for free 188 Re. No accumulation in liver and other organs was noted. Effective half-time of 188 Re-zoledronic acid in bone metastases was 7.14 ± 0.7 h, in normal bone 6.14 ± 0.5 h. Urinary excretion of 188 Re-zoledronic acid occurs mostly after 4 h p/a and contains 10-15% of injected radioactive substance. Two patients had transient thrombocytopenia down to 101 × 10 9 , having been continuing for 2 weeks, other blood cells were not affected. One patient had no thrombocytopenia at all. Two patients had flash-syndrome on the second day, which did not need additional analgesic administration. All patients noted significant reduction of pain and consumption of painkillers. No other side effects were noted.
Conclusion: 188 Re-zoledronic acid is a very promising radiopharmaceutical for bone palliation therapy which combines features of two most effective bone palliation therapy methods. Further investigations will be performed.
Radiosynoviorthesis in Joints Less Frequently Affected With Arthropathy After the Failure of Previous Treatment
M. Vereb, L. Kaliská, K. Liepe
Klinikum Kassel, Nuklearmedizin, GH Kassel, Germany
Aim of the Study: Radiosynoviorthesis (RSO) is a local intra-articular injection of radionuclide in colloidal form in order to treat the synovitis in affected joints. Firstly used by Fellinger et al. in 1952, the technique has now been applied for more than 50 years for the treatment of resistant synovitis of individual joints after the failure of long-term systemic pharmacotherapy and intra-articular steroid injections. It is safe, accepted, and well documented procedure, which is routinely used in rheumatic and psoriatic arthritis and also in other different types of joint diseases as mono-, oligo-, and polyarthritis, haemophilic arthritis, pigment villonodular synovitis, lyme borreliosis. Commercially, available radionuclides are: Ytrium-90, recommended for knees; Erbium-169 recommended for metacarpal/metatarzophalangeal and interphalangeal joints; Rhenium-186 recommended for hip/shoulders, elbow, wrist/ankle and subtalar joints. According to literature the improvement of joint pain after RSO was noticed in period longer than 2 years in 40-90% of cases, depending on affected joint and type of arthropathy. Our target is to evaluate the effectiveness of RSO in less frequently affected joints like acromioclavicular and sternoclavicular joints.
Materials and Methods: Painful inflammatory joint disease was confirmed by hyperperfusion on two-phase bone scintigraphy. Thirty-three acromioclavicular joints and three sternoclavicular joints were enrolled into the study. A total of 37 MBq of Rhenium-186 in volume of 0.2 - 0.4 ml was injected intra-articularly under C-Arm Fluoroscopy, in supine position. After Rhenium-186 application the upper limb was immobilized by triangular scarf for period of 2 days. The evaluation of positive effect of RSO was measured by subjective consideration of patient about the pain relief (according to 10° visual analog scale [VAS] of pain). As an acceptable result we considered the pain reduction at least in 2° of VAS. Two-phase bone scintigraphy was performed in 3 months interval after RSO, in order to provide an objective proof of good result of RSO, where the improvement of hyperperfusion of selected joints was recorded.
Results: A total of 33 acromioclavicular joints in 28 patients and 3 sternoclavicular joints in 2 patients were injected in period of 7 years. Tolerance of RSO in selected joints was excellent in all patients. No complications were observed after injection of radionuclide Rhenium-186. All patients reported early pain relief in 7 days after RSO, which started usually on second day after injection and lasted minimally for 3 months. The objective evaluation of therapy by two-phase bone scintigraphy confirmed sufficient effect of therapy. The reinjection of radionuclide due to recurrent pain or positive perfusion on two-phase bone scan was performed in five patients with affected acromioclavicular joints and in one patient with affected sternoclavicular joint, in time interval of more than 2 years.
Conclusion: Our results confirmed the good clinical efficacy of Rhenium-186 synoviorthesis of less frequently affected joints with arthropathy after failure of previous treatment. Application of Rhenium-186 into selected joints was followed by prompt pain relieve that lasted minimally for 3 months or longer. No side effects were observed. In conclusion, we can state that RSO of less frequently affected joints is comparatively effective as RSO in other joints, which are frequently treated in daily practice.
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