|Year : 2013 | Volume
| Issue : 4 | Page : 232-267
Abstracts of Posters
|Date of Web Publication||18-Oct-2013|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Abstracts of Posters. World J Nucl Med 2013;12, Suppl S2:232-67
Dual-Phase Tc99m MIBI Scintigraphy in Lymphoma as a Predictor of Response to Chemotherapy
Z. Chiragh, A. Fatima, S. Fatima
Nuclear Medicine, Nawaz Sharif Social Security Hospital, Lahore, Pakistan
Aim of the Study: Failure of chemotherapy is a major issue faced by treating physicians for otherwise effectively treatable lymphomas. This study aimed to determine the role of dual-phase Tc-99m MIBI scintigraphy for predicting response in patients receiving chemotherapy for lymphomas and to correlate the uptake ratios and retention index % (RI%) with various prognostic markers.
Materials and Methods: Histologically proven lymphoma patients from both genders and all age groups were studied. Dual-phase Tc-99m MIBI scintigraphy (pre-chemotherapy) was performed at 10 min and at 3 h.
Results: A total of 24 lymphoma patients (17 male and seven female), mean age 42 ± 21.95 years, were enrolled in the study. The pre-chemotherapy tumor/background ratios (T/B ratios) and RI% were calculated from the 25 lesions visualized by Tc-99m MIBI scintigraphy. A computed tomography (CT) scan picked up 32 lesions. Chemotherapy response was evaluated at the end of three cycles and a CT scan was performed to compare the reduction in lesion size.
Conclusion: Dual-phase Tc-99m MIBI scintigraphy can be a helpful, non-invasive tool to predict the chemotherapy response in lymphoma patients.
Post-Synthesis of a new [64Cu]-Porphyrin Complex on Silica MCM-41 as a New Radiopharmaceutical Delivery System
Y. Fazaeli, M. Aboudzadeh
Nuclear Medicine, Agricultural, Medical and Industrial Research School, Moazen Blvd, Karaj, Iran
Aim of the Study: The biocompatibility of nanoporous MCM-41 with and without surface functionalization has been assayed in different procedures. The goal of this research was to investigate the potential of a newly synthesized copper-64 complex; [ 64 Cu] 5,10,15,20-tetrakis (penta fluoro phenyl) porphyrin.
Materials and Methods: The copper-64 complex was synthesized and grafted on mesoporous silica MCM-41. We evaluated the biodistribution of the copper-64 complex and the grafted one on MCM-41 in rats bearing fibrosarcoma tumor as a model system. Stability of the complex and that of the grafted one was checked in the final formulation (in case of undesired release of the grafted complex, nanocompound under physiological conditions) and human serum for 24 h. The biodistribution of the labeled complex and that of the nanocompound in the vital organs of Sprague Dawley rats was studied.
Results and Conclusion: Using the MCM-41 drug delivery system made the [ 64 Cu]-labeled complex a strong tracer for detecting the growth of cancer cells at very low concentrations. Furthermore, the animal tests and imaging revealed a high uptake of the nanocompound in tumor cells.
Radio Synthesis of a New [ 201 Tl]-Porphyrin Complex as an Imaging Agent
Y. Fazaeli, A. Jalilian, M. Aboudzadeh
Nuclear Medicine, Agricultural, Medical and Industrial Research School, Moazen Blvd, Karaj, Iran
Aim of the Study: Because of the interesting physical properties and wide availability of thallium-201 as a single-photon emission computed chromatography (SPECT) radionuclide and the importance of porphyrin derivatives as biological carriers such as low toxicity, tumor avidity and rapid wash-out, the idea of incorporation of this nuclide into porphyrin derivatives was targeted.
Materials and Methods: [ 201 Tl (III)]- labeled 5,10,15,20-tetrakis (pentafluorophenyl) porphyrin ([ 201 Tl (III)]-PFPP) was developed in this work using freshly prepared [ 201 Tl (III)]TlCl 3 and 5,10,15,20 tetrakis (pentafluorophenyl) porphyrin (H2PFPP) for 60 min at 100 o C (radiochemical purity: >99% ITLC, >99% HPLC, specific activity: 13-14 GBq/mmol). Stability of the complex was checked in the final formulation and human serum for 48 h. The partition coefficient was calculated for the compound (log P = 1.92). The biodistribution of the labeled compound in the vital organs of wild-type rats was studied using scarification studies and SPECT up to 24 h.
Results and Conclusion: The complex is mostly washed out from the circulation through the kidneys and liver.
Indium-111 Maltolate Complex as a Cell-Labeling Agent for SPECT Imaging
Y. Fazaeli, A. Jalilian, M. Aboudzadeh, G. Aslani
Nuclear Medicine, Agricultural, Medical and Industrial Research School, Moazen Blvd, Karaj, Iran
Aim of the Study: Because of the cell-labeling potentials of various metal-maltol complexes, the idea of developing a possible cell-labeling imaging agent using single-photon emission computed chromatography (SPECT) with [ 111 In]-maltolate complex has been investigated.
Materials and Methods: [ 111 In]-labeled 3-hydroxy- 2-methyl-4H-pyran-4-onate ([ 111 In]-maltolate) was prepared using freshly prepared [ 111 In] InCl 3 and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form for 25 min at 45 o C. Stability of the complex was checked in the final formulation and human serum for 48 h. The partition coefficient was calculated for the compound followed by biodistribution and imaging studies.
Results: [ 111 In]-maltolate was successively used in the radiolabeling of red blood cells for diagnostic studies. The complex was prepared successfully (radiochemical purity: >98% ITLC, >98% HPLC, specific activity: 15-17 GBq/mmol, log P = 0.278). The complex is mostly washed out from the circulation through the kidneys in 24 h. The cell-labeling efficacy was significant at the time of the experiment.
Conclusion: [ 111 In]-maltolate can be an interesting cell-imaging agent due to the stability and cell avidity of metal-maltol complexes; however, further biodistribution studies in various cells as well as diagnostic protocols is necessary.
SPECT Imaging of Blood Pool in Rabbits using PEG-Nano Liposomes Labeled with 99m Tc-HMPAO
K. Sadri, M. R. Jafari, V. R. Dabbagh, S. Momenypoor, S. Barati, F. Johari, S. R. Zakavi
Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Ahmad Abad, Ghaem Hospitol, Mashhad, Iran
Aim of the Study: In vitro labeling of red blood cells (RBCs) with 99m Tc is a cumbersome procedure and may increase the risk of blood contamination; hence, there is always a need for a safe, convenient and stable alternative blood pool imaging agent. Conventional liposomes are rapidly taken up by the cells of the mononuclear phagocyte system (MPS), primarily those located in the liver and spleen. By decreasing the liposome size and modifying their formulation with polyethylene glycol (PEG), the blood pool circulation time will increase, giving the opportunity of blood pool scintigraphy.
Materials and Methods: PEGylated nano-liposomes were prepared with HSPC, cholesterol and DSPE-mPEG 2000 (12.5:8:1.2 molar ratios). In order to enhance the blood circulation time, nano-liposomes were produced using an extrusion technique. The 99m Tc-hexamethylpropylene-amine oxime ( 99m Tc-HMPAO) complexes were used for radiolabeling of the PEGylated liposomes. Single-photon emission computed chromatography images were acquired using a 256 × 256 matrix for a total of 300,000 counts immediately and 2 and 24 h following 99mTc-nano-liposome injection into the ear vein of the rabbits. ROI s have been drawn over the heart, liver, spleen and background.
Results: PEGylated nano-liposomes showed an increase in blood pool circulation (7.7%ID/g at 1 h and 4.9%ID at 4 h), with a decreased accumulation in the liver (12%ID/g at 1 h and 14%ID/g at 4 h). The ROI ratios for heart to liver, heart to spleen and heart to background were 1.25, 4 and 4.28 at 2 h, which changed to 1.06, 1.75 and 2.51 at 24 h.
Conclusion: PEGylated nano-liposomes have the potency of evading the MPS system and, therefore, have a prolonged circulation time in blood. This finding would lead us to the potential use of liposomes in blood pool imaging.
Prognostic Value of FDG Uptake of Primary Tumor and Metastatic Lesions in Advanced Non-Small Cell Lung Cancer
X. C. Nguyen, V. K. Nguyen, M. T. Tran, S. Maurea, M. Salvatore
Unit of PET/CT and Cyclotron, Cho Ray Hospital, 201 B, Nguyen Chi Thanh, Ho Chi Minh City, Vietnam
Aim of the Study: To assess the prognostic value of maxSUV of primary tumor, maxSUV of whole body tumors and metabolic tumor burden as sumaxSUV by sum of the maxSUVs of primary tumor, metastatic lymph nodes and metastatic lesions per organ on FDG-PET/CT in patients with advanced non-small cell lung cancer (NSCLC).
Materials and Methods: Eighty-three consecutive patients (49 male, 34 female; age 58.9 ± 11.0 years) with advanced NSCLC were enrolled in the study. Seventeen patients had stage IIIA, 21 had stage IIIB and 45 had stage IV. MaxSUV of primary tumor (maxSUVpt), maxSUV of whole body tumors (maxSUVwb), sumaxSUV and other factors such as age, gender, tumor cell type, T stage, N stage, overall stage, primary tumor size and specific treatment were analyzed for correlation with overall survival. The median follow-up duration was 13 months (range, 4-31 months).
Results: Fifty (60.2%) of the 83 patients were dead during a median follow-up time of 11 months, and 33 patients (39.8%) were alive with a median follow-up time of 15 months. Univariate analysis revealed that overall survival was significantly correlated with sumaxSUV (≥35 vs. <35, P = 0.004), T stage (T4 vs. T1-T3, P = 0.025), overall stage (IV vs. III, P = 0.002), gender (male vs. female, P = 0.029) and specific treatment (no vs. yes, P = 0.011). MaxSUVpt and maxSUVwb were not found to be correlated with overall survival, with a P value of 0.139 and 0.168, respectively. Multivariate analysis identified sumaxSUV, T stage, gender and specific treatment as independent prognostic indicators in advanced NSCLC. Patients with a sumaxSUV of ≥35 were 1.921-times more likely to die from NSCLC than those with a sumaxSUV of <35 (P = 0.047). The median survival time was 14 months for patients with a sumaxSUV ≥35 compared with 20 months for those with a sumaxSUV <35. In patients with metastatic NSCLC, sumaxSUV with a cut-off of 35 was much more significant for survival prognosis (P = 0.021).
Conclusion: SumaxSUV is a new prognostic measure, independent of tumor stage, gender and specific treatment, in advanced NSCLC. SumaxSUV may be better than maxSUV of primary tumor and maxSUV of whole body tumors in the prediction of survival in advanced NSCLC. A large prospective cohort study is necessary to validate these results.
Feasibility Study for Neodymium-140 ( 140 Nd) Radioisotope Production and its Purification using Nano-Resin
M. Aboudzadeh, Y. Fazaeli
Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School, Moazen, Tehran, Islamic Republic of Iran
Aim of the Study: 140 Nd (T1/2 = 3.37 d, EC 100%, no y) decays into the short-lived daughter 140 Pr (Ti/2 = 3.4 min, Ep+ = 1.1 MeV), which has a high positron emission rate of 50%. This daughter isotope decays via positron emission (51% β+, Emax¾ 2.3 MeV) to stable 140 Ce. Neodymium-140 has some unique nuclear properties and seems to be suitable for most of the usual treatments in ERT. The 140 Nd/ 140 Pr system provides an ideal in vivo radionuclide generator for diagnostic applications with PET.
Materials and Methods: In this work, 140 Nd excitation functions via 141 Pr (p, 2n) 140 Nd, 141 Pr (d, 3n) 140 Nd, 140 Ce (3He, 3n) 140 Nd and 140 Ce (4He, 4n) 140 Nd reactions were calculated by ALICE 2002, ALICE/ASH and TALYS 1.0, with the data taken from the TENDL-2010 database. After the Peruse Cyclotron facility, the 141 Pr (p, 2n) 140 Nd reaction was selected to be the appropriate reaction for producing neodymium. Thickness of the targets was calculated using the SRIM 2010 code. Targets consisted of 250 mg Pr 2 O 3 , and were compressed into pellets and irradiated using beam currents of 20 μA and an irradiation period of 1.5 h. After bombardment, a purification process was carried out by means of newly synthesized nano resins.
Results and Conclusion: For Ep: 23→11 MeV, the integral yield is obtained 6.5 mCi/μA.h (240.5 MBq/μA.h).
Production of Industrial Zinc-62/Copper-62 Generator for PET Purposes
Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School, Moazen, Karaj, Iran
Aim of the Study: In this research, after evaluation of the various nuclear codes, the suitable reaction natCu (p, xn) 62 Zn and the target material were chosen and a natural copper coating was performed with an optimized diameter.
Materials and Methods: The best method for structuring the target regarding the conditions and also the proton bombardment parameters (energy, currency density and bombardment time) were defined. At the next step, after the bombardment process, 62 Zn purification from natural copper and the other possible impurities was performed using chromatographic methods. Then, the quality control processes were performed completely on the product. The isotope of 62 Zn was grafted on a suitable column and used in the standard type A generators.
Results and Conclusion: The results confirmed the production of Zinc-62 with 5 Curie activity and 99.99% purity. Finally, the produced Copper-62 was labeled successfully with the pharmacy PTSM legend.
Radioiodine Ablation of Thyroid Remnants in Patients with Differentiated Thyroid Carcinoma
S. R. Miah, R. Islam, S. Sharmin
Institute of Nuclear Medicine and Allied Sciences, Bangladesh Atomic Energy Commission, Comilla Medical College Campus, Comilla, Bangladesh
Aim of the Study: The aims of the study were to evaluate the efficacy of high-dose radioiodine therapy in patients with differentiated thyroid carcinoma and to determine the impact of thyroid remnant volume on proper ablation.
Materials and Methods: A retrospective analysis of 71 differentiated thyroid carcinoma patients treated with high-dose radioiodine ( 131 I) for post-surgical ablation of the thyroid remnants was performed in the Institute of Nuclear Medicine and Allied Sciences, Comilla of Bangladesh Atomic Energy Commission, of which there were 60 females and 11 males, with a female-male ratio of 5.5:1. All patients were enrolled during the period from January 2001 to December 2011. The age range of the patients was 15 years to 90 years. The radioiodine ( 131 I) ablation therapy doses ranged from 30 mCi to 200 mCi. The selection of treatment dose was based on surgical and pathological findings as well as thyroid remnant volume determined by Single-photon emission computed chromatography scintigraphy. A successful ablation was defined as the absence of activity in the thyroid bed on subsequent imaging studies.
Results: Fifty-nine patients (83.1%) showed complete ablation and 12 patients (16.9%) showed partial ablation of the thyroid remnants after radioiodine therapy. The remnant thyroid volume determined from the scintigraphic images was significantly different (P = 0.048) between those patients who were completely ablated and those who were partially ablated. It was also shown that in complete ablation, 52.5% of the patients had thyroid remnant volume <1.0 g, 40.7% had 1.1-2.0 g, 5.1% had 2.1-3.0 g and 1.7% had >3.0 g.
Conclusions: Successful ablation of the thyroid remnants significantly depends on their volume. The smaller the volume of the thyroid remnant, better is the response and the larger the volume of the thyroid remnant, poorer is the response to radioablation therapy, i.e. the successful ablation of the thyroid remnant is inversely related to the thyroid remnant volume.
Preparation of 99m Tc-Labeled Methotrexate by a Direct Labeling Technique as a Potential Diagnostic and Response Monitoring Agent for Breast Cancer
Nuclear Medicine, GINUM, Gujranwala, Pakistan
Aim of the Study: Methotrexate (MTX) is being used in clinical oncology for the treatment of a wide variety of cancers. The aim of the present study was to directly label MTX with 99m Tc using Sn/pyrophosphate as a reducing agent and to use this labeled compound as a potential anticancer radiopharmaceutical for breast cancer imaging and therapy monitoring during chemotherapy.
Materials and Methods: We studied the labeling efficiency of the 99m Tc-MTX compound by paper chromatography and instant thin-layer chromatography (ITLC) in acetone and saline, and found it to be more than 95%. The in vitro stability of the labeled MTX in serum was studied up to 5 h. The partition coefficient in n-octanol and saline indicated that the labeled radiopharmaceutical was hydrophilic. We then tested 99m Tc-MTX in five breast cancer patients.
Results: Protein-bound 99m Tc-MTX showed rapid clearance from blood. The biodistribution data suggested that 99m Tc-MTX was cleared by the kidneys and the liver. Patients' data also showed a highly significant uptake of 99m Tc-MTX in breast cancer.
Conclusion: This study indicated that 99m Tc-MTX may be used as a potential diagnostic agent for the imaging of breast cancer patients, and may show treatment efficiency in case MTX is to be used for treatment.
Bone Metastasis from Differentiated Thyroid Carcinoma: Diagnosis, Treatment and Outcome Experience of a Tunisian Center
K. Chatti, N. Essabbah, H. Regaieg, T. Kamoun, R. Sfar, M. Nouira, M. Ben Fredj, N. Ayachi, H. Essabbah
Department of Nuclear Medicine, Sahloul Hospital, Route de ceinture, Sousse, Tunisia
Aim of the Study: The bone is the second most frequent target of distant metastasis in patients with differentiated thyroid carcinoma (DTC). Many authors reported that it decreased the 10-year survival by 30%. The aim of our study is to report the diagnosis, treatment and outcome of patients with bone metastasis (BM) from DTC treated in the Department of Nuclear Medicine of Sousse (Tunisia).
Materials and Methods: We retrospectively reviewed patient data with BM from DTC in the University Hospital of Sahloul, Sousse, Tunisia. There were 844 patients with DTC from 1992 to 2012. Among them, 16 patients had BM. All the patients were adults with a mean age of 54 ± 14 years. The majority of participants were women (14/16).
Results: BM was present in 2% of DTC. They were synchronous in 12 and metachronous in four, with a 1-8 years' delay. All the patients had had total thyroidectomy. Twelve of 16 patients had had lymph node resection. There were four cases with papillary DTC; in one case with tall cell and in one case where no tumor was detected in the thyroid. There was vesicular DTC in 10 cases, wherein lymph node resection was performed in seven cases that was positive in two cases. All but three of the patients with BM were symptomatic. Thyroglobulin was higher than 200 ng/mL in 15/16 patients. In one patient this level was less than 3 ng/mL. The diagnosis of BM was essentially made by radioiodine scintigraphy. Only two cases of BM were non-functional, and the diagnosis was based on the other imaging techniques and/or anatomo-pathology. In 14 cases, the treatment was radioiodine associated with surgery, in eight cases with or without external radiotherapy and to external radiotherapy in six cases. The 5-year survival rate was 85% and that for 10 years was 50%.
Conclusion: BM from DTC was rare. It had decreased the 10-year survival by 50%. In our population, the surgery and external radiotherapy associated with radioiodine had increased the overall survival.
Effectiveness and Thyroid Functional Status after Radioiodine Therapy for Thyrotoxicosis: A Retrospective Study
M. Hossain, K. Shah, N. Laz, P. Ahmed, T. Ahmed, R. Islam, S. Islam Chowdhury
Centre for Nuclear Medicine and Ultrasound, Rajshahi, Bangladesh
Aim of the Study: Thyroid disease is near to endemic in the North Western part of Bangladesh, which is located quite far from the "Bay of Bengal." Different treatment options are available for the treatment of thyrotoxicosis, like antithyroid drug, surgery and radioactive iodine (RAI) therapy. But, RAI therapy is now being considered as the treatment of choice for thyrotoxicosis in this area, like other countries of the world, due to its easy administration and cost-effectiveness. Recently, this treatment is being given regularly in the North Western part of Bangladesh. This retrospective study was performed to determine the efficacy and outcomes of the thyroid functional status of radioiodine therapy for thyrotoxicosis.
Materials and Methods: This study was performed at the Centre for Nuclear Medicine and Ultrasound (CNMU), Rajshahi, situated in the North Western part of Bangladesh, which covers the radioiodine therapy of 10 districts surrounding this center for thyrotoxicosis. A total of 410 patients with thyrotoxicosis were treated by radioiodine during the period from January 2006 to December 2011, and 45/410 patients were followed-up to determine the efficacy and outcome of thyroid functional status after therapy. All patients were evaluated for any cardiac disease before treatment. We used 10-15 mCi of radioiodine as a fixed dose regimen.
Results: This study showed that use of radioiodine therapy is increasing daily for thyrotoxicosis. A total of 410 patients were treated during the period from January 2006 to December 2011. Of them, 41 were treated in 2006, 62 were treated in 2007, 67 were treated in 2008, 68 were treated in 2009 and 2010 and 104 patients were treated in 2011 (M:F = 0.8:1; age range = 15-70 years, mean ± SD = 42 ± 15 years). Of the 410 patients, 45 patients were followed-up for 1 year, and we found that 66.7% turned into hypothyroidism, 25% into subclinical hypothyroidism and 8.3% remained as euthyroid state. Only 16.6% of the patients required a second dose.
Conclusion: Radioiodine therapy is now the most useful method for the treatment of thyrotoxicosis for its easy administration and low cost, and its use is increasing daily in the North Western part of Bangladesh. Therefore, a further study will be beneficial for this treatment and will thereby help to improve the health status of Bangladesh as well as reduce the economic loss.
Details of Histopathology in Patients with One or More First-Degree Relatives who have Well-Differentiated Thyroid Cancer
S. Frangos, A. Vanezi, A. Savva, A. Rousounidou, A. Patsali
Nuclear Medicine, Bank of Cyprus Oncology Center, Acropoleos 32, Strovolos-Nicosia, Cyprus
Aim of the Study: Familial non-medullary thyroid cancer (FNMTC) may develop with no obvious associated pathogenetic factors. The prevalence of FNMTC is around 6% of thyroid cancers. This tends to be more aggressive than the sporadic form. It is associated with an earlier age at diagnosis, a higher ratio of male to female, a greater incidence of spread outside the thyroid gland and a greater rate of persistence/recurrence. We identified the patients in our clinic with one or more first-degree relatives (FDR) with WDTC. A FDR is defined as a close blood relative, i.e. the patient's parents, full siblings or children. The details of histopathology (HP), such as multifocality, tumor diameter, presence of thyroiditis, lymph node metastases and tumor stage, were investigated.
Materials and Methods: Among the 942 patients followed-up in our Thyroid Cancer Clinic, we identified 58 (47 F and 11 M) with FDR (6.15%) belonging to 25 families. The histopathology of 52 of these 58 patients is available. The mean age at diagnosis was 40.1 years (range, 14-71 years). Thirty-five of the patients had one and 17 patients have two FDRs.
Results: The histopathology showed that 49 patients had papillary carcinoma, three patients had follicular carcinoma and 11 patients had Hashimoto thyroiditis; the average tumor size was 10 mm. Thirty-two patients underwent lymph node dissection (between one and 31 nodes were removed). Lymph node metastasis was found in 14/32 of these patients. Eighteen (18) patients showed multifocality. Eight (8) patients showed the co-existence of adenoma.
Conclusion: The majority of the studied patients showed multifocality, presence of thyroiditis and lymph node metastases, which are associated with FNMTC. Patients with the above histopathology should be advised to consider having screening of their FDRs.
Utility of 99m Tc HYNIC-TOC in the Evaluation of Neuroendocrine Tumor (NET): A Pictorial Review
A. Shinto, K. Kamaleshwaran, N. Sudhakar, P. Sudhakar, M. Sairam, Subramaniam
Nuclear Medicine, KMCH, Avanashi Road, Coimbatore, India
Aim of the Study: To explore the utility of whole body scintigraphy using 99m Tc HYNIC-TOC and single-photon emission computed tomography (SPECT) in the detection and staging of primary and metastatic neuroendocrine tumors (NETs).
Materials and Methods: Thirty patients (age group 7-75 years) with histopathologically proven tumors, who did not receive any therapy (GEPNET-8, carcinoids-12, gastrinomas-8 and NETs of unknown origin-2) were investigated. Whole body scintigraphy was performed 1-2 h after the IV administration of 370-555 MBq (10-15 mCi) 99m Tc HYNIC-TOC. In all the cases, a SPECT-computed tomography (CT) of the relevant region and of the equivocal lesions, if any, were performed with a dual-headed camera enabled with a dual-slice diagnostic CT
Results: All treatment-naive patients demonstrated SSTR positivity and were divided according to the Rotterdam scale from 1 to 4. SPECT/CT helped to localize regional tumor stage, nodal involvement, quantify hepatic metastases and identify distal metastases, especially skeletal.
Conclusion: 99m Tc-HYNIC-TOC is highly useful for the in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy, especially for patients with inoperable disease. SPECT/CT imaging improves the sensitivity and specificity of the images and markedly reduces the indeterminate findings.
Biodistribution Imaging Study in Rats after Intra-Articular Administration of 90 Y-Labeled Tin Fluoride Colloid
L. Jaukovic, D. Jankovic, N. Nikolic, S. Vranjes-Djuric, B. Ajdinovic
Military Medical Academy, Vinca Institute of Nuclear Science, Institute of Nuclear Medicine, Laboratory for Radioisotopes, 17 Crnotravska, Belgrade, Serbia
Aim of the Study: Yttrium-90 is a pure β-emitting radionuclide with a high energy (Emax = 2.28 MeV) and a short half-life (T = 64.1 h). It has shown to be a promising isotope to use in radionuclide therapy. Particle size, shape, charge and stability of a radiocolloid suspension are significant parameters that determine its organ distribution in vivo. The aim of this study is to investigate the biodistribution of 90 Y-tin fluoride colloid ( 90 Y-SnF-c, particles >1 μm) for possible application in radiosynovectomy (RS). The SnF-c was prepared, radiolabelled with 90 Y and characterized with respect to its physicochemical properties and biological behavior in an animal model.
Materials and Methods: Male Wistar rats were used (three per time point), with a body weight of 300-350 g and aged 8 weeks old. Rats were injected intra-articularly with sterile 90 Y-SnF-c particles >1 μm, at a dose volume of 0.2 mL and a dose activity of 18.5 MBq in the knee joint. The knee was kept immobile for 1 min and then moved a few times. Animals were imaged using a single-head gamma camera (Searle) with medium-energy general purpose collimator in 64 × 64 × 16 matrix size without zooming. The energy peak setting (window width 50%) was 75 keV for 111 In - adequate for characteristic X-ray and "bremsstrahlung" imaging. The sequential images were recorded at 2, 24, 48 and 96 h after injection and the count rate in the selected regions of interest was compared. To determine a possible leakage of 90 Y-SnF-c particles injected intra-articularly, the animals (three per time point) were sacrificed at different times (1, 24, 48 and 96 h) and their organs were removed, treated and counted.
Results: Scintigraphic images of the knee regions of the rats showed the activity remaining in the knee joint at 96 h after intra-articular administration. No leakage to the inguinal lymph node or other lymph nodes could be observed as a function of time. In the whole body scans, no other activity distribution was seen anywhere in the body. Biodistribution studies showed that activity remained in the knee joint at 96 h, which was over 98% of the injected activity, with no significant levels being detected in the other tissues or organs, including the liver, spleen and skeleton.
Conclusion: The present study has shown that 90 Y-SnF-c can be prepared with a high in vivo stability and controllable particle size. Promising results of in vivo experiments suggest that 90 Y-SnF-c (particles >1 μm) may be of potential use for RS.
I-131 Capsule versus Liquid: A Comparative Study and Clinical Usefulness in Thyroid Carcinoma Patients - Quantitative and Dosimetric Evaluation
Om Prakash, R. Tiwari, S. Rach, N. Patel, V. Patel, M. Soni, V. Bhatt, R. K. Vyas
Gujrat Cancer and Research Institute, New Civil, Ahmedabad, Gujrat, India
Aim of the Study: The objective of this study was to compare the ablation rate and side-effects with high-dose radioiodine (I-131) capsule and liquid formulations. Capsule and liquid radioiodine (I-131) are routinely used in the treatment of differentiated thyroid carcinoma. In the thyroid tissue, it accumulates 17-25 times more than the other parts of the body. It exerts a cytotoxic effect on the thyroid tissue by beta emission. I-131 is an isotope of I-127, which is a beta and gamma emitter. Its maximum beta energy is 0.61 MeV and its average energy is 0.192 MeV. It is a byproduct of uranium and plutonium fission.
Materials and Methods: All the capsule and liquid radioiodine was procured from BRIT, Bhabha Atomic Research Centre, Mumbai. All the patients fasted for at least 8 h or overnight before the dose and 1 h after the dose. More than 300 patients were included in this study. Before large-dose therapy, all the patients were given 1-2 mCi I-131 and gamma imaging was performed with a dual-head gamma camera using a high-energy. One hundred and fifty patients received liquid iodine and 150 patients received the capsule formulation. Images were taken at 30 min and 1, 2, 3 and 4 h.
Results: The liquid form of I-131 was absorbed from the stomach within 15-30 min, but the capsules dissolved slowly and their shape was maintained for up to 2 h after administration. Because of the slow absorption rate of the capsule formulation, the mucosal lining of stomach gets a very high radiation dose from 100 mCi; the dose to the stomach wall was approximately 448 rad or 4.48 Gy/h. On the other hand, liquid I-131 delivered a much lower dose to the stomach. After administration of I-131 therapy, the patients were kept in an isolation ward. Common complaints from both types of formulation (liquid and capsule) were nausea, vomiting, neck pain and abdominal pain. But, in our observation, we found that those patients who have received a capsule reported higher abdominal pain. Calculations showed that the dose to the stomach from the capsule was approximately 6-10 Gy. Because of this radiation injury, the mucosal lining damage occurred, and replacement of the mucosal lining takes place in 5-10 days. This was the reason for the abdominal pain in patients administered the capsule formulation.
Conclusion: This quantification and dosimetric evaluation suggests that liquid I-131 is better tolerated by patients with quicker absorption and less dose to the abdomen and less gastric pain, although liquid handling needs extra care and more radiation exposure to the occupational worker.
Perspectives of Availability of Therapeutic Radioisotopes
V. R. Hernan
Director's Office, Bolivian Institute of Nuclear Research and Technology, Av. Villazón 1245, La Paz, Bolivia
Abstract: Radioisotopes with nuclear decay characteristics for application in therapeutic nuclear medicine have demonstrated therapeutic effectiveness in a variety of clinical conditions in the last decades. In fact, therapeutic effectiveness has been seen since the use of 32P and 131I in the dawn era of nuclear medicine in the first part of the 20 th century. Today, radioisotopes with nuclear decay characteristics are becoming more widely utilized, with the availability of newer radioisotopes produced in research reactors and cyclotrons facilities. However, although their availability is somehow more secured in the industrialized countries, in the developing world, this is far from certain in spite of the fact that many of them operate both facilities. The reason for this situation is varied, ranging from the complexity of the technology and the economics of the radioisotope and radiopharmaceutical production, to a lack of qualified manpower as well as a lack of the primary driving force, which is insufficient awareness of the nuclear medicine physicians. Many of the operating reactors and cyclotrons in the developing countries of Africa, Asia, Latin-American and Eastern Europe have characteristics in terms of neutron fluxes or beam energies and intensities appropriate for the production of therapeutic radioisotopes such as 153Sm, 186Re and 177Lu in the case of research reactors or 111In, 64-67Cu, 86Y, 124I, 211At, 225Ac and others in the case of cyclotrons. This presentation will discuss the hurdles needed to be overcome in the situation of developing countries to make available to the medical community a palette of radioisotopes for successful and affordable application of RIT, make a critical assessment of the possibilities of the available reactors and cyclotrons to effectively produce therapeutic radioisotopes and propose strategies to realistically improve their availability.
Life Quality Evaluation in Patients with Differentiated Thyroid Cancer: Is SF-36 Appropriate for this Purpose?
N. K. Ayati, S. R. Zakavi, S. Zare
Nuclear Medicine Research Center, Mashhad University of Medical Science, Mashhad, Iran
Aim of the Study: Differentiated thyroid cancer (DTC) is a common malignancy in the young population. Different characteristics of this entity necessitate special attention to the quality of life (QoL) of these patients. This malignancy generally has a very good prognosis, with a >90% long-term survival. Consequently, life quality improvement is the first priority in the management of these young survivors. Also, the classic management of a new DTC case includes surgery, iodine therapy, whole life medical therapy and, occasionally, external beam radiotherapy. Each of these therapeutic modalities can significantly affect the QoL of the patients. In this study, we investigated the QoL in DTC patients.
Materials and Methods: Two hundred consecutive DTC patients who had undergone thyroidectomy and radio-iodine therapy and were under long follow-up in our nuclear medicine research center were studied using the Short Form 36 Health Survey (SF-36). Also, in addition to SF-36, we asked seven questions specific to the problems of the DTC patients. The study was approved by the Ethics Committee of the university hospital.
Results: One hundred and sixty-five (82.5%) female and 35 (17.5%) male patients, aged 12-84 years (mean ± SD = 42.3 ± 14.7 years) were included in the study. Seventy-one percent of the patients reported fair to excellent general health. The overall physical (PF) and social (SF) functioning were not statistically different from the general population (P = 0.158 and 0.842, respectively). Also, PF and SF did not show a significant difference in the different cancer stages. Patients showed a statistically significant difference with the general population in five out of the seven specific questions related to usual DTC problems.
Conclusion: General QoL questionnaires (such as SF-36) are not able to evaluate the specific problems and limitations of DTC patients. They have to be modified based on the common complaints of DTC patients. The non-fatal nature of thyroid cancer with excellent long-term survival requires developing a specific questionnaire for QoL evaluation in these patients.
Thyroid Volume Changes on Ultrasonography as a Predictor of Radioiodine Therapy Outcome in Hyperthyroidism
N. K. Ayati, S. R. Zakavi, Z. Mousavi, B. Davachi, S. Zare
Nuclear Medicine Research Center, Mashhad University of Medical Science, Mashhad, Iran
Aim of the Study: Radioactive iodine (RAI) administration is a well-established treatment in hyperthyroidism. Many studies support the hypothesis that RAI can result in thyroid volume reduction. This study investigated the relationship between thyroid volume changes and the responsiveness of thyroid tissue to RAI administration.
Materials and Methods: Forty-three consecutive hyperthyroid patients who were referred for radioiodine therapy were included in our study. The administered radio-iodine dose per gram of thyroid tissue ranged from 100 to 200 uCi/g. Thyroid volume was measured by ultrasonography before and 1 and 3 months post-RAI administration. Responsiveness was defined as hypothyroidism, subclinical hypothyroidism or euthyroidism, and was assessed by the evaluation of clinical and paraclinical parameters at the end of the first and third months post-treatment.
Results: Forty-three patients (39 female and four male) were studied with a mean age of 40.9 ± 16.4 years. Multinodular goiter was seen in 72.1% of the patients and diffuse goiter was seen in 27.9% of the patients. The mean 24-h radio-iodine uptake was 55.7 ± 17.6%. The total iodine dose ranged from 1.5 to 30 mCi, with a mean activity of 9.0 ± 7.8 mCi. Patients were followed-up for a mean of 3.9 ± 2.1 months, with a rate of 97.6% at 1 month and 90.7% at 3 months. Thyroid weight (on palpation) was significantly decreased from 44.3 ± 23.2 g to 35.8 ± 21.1 g 1 month after therapy (P = 0.002). Using ultrasonography, the thyroid volume was significantly decreased from 29.8 ± 18.0 g to 25.1 ± 20.2 g at 1 month after therapy (P = 0.02) and to 21.6 ± 18.3 g at 3 months after radio-therapy (P = 0.001). Response rate was seen in 66.6% of the patients at 1 month and 76.9% of the patients at 3 months. The mean thyroid volume change at 1 month (using ultrasonography) in patients who responded to therapy was 4.9 ± 8.7 mL, while it was −0.65 ± 3.7 mL in patients who did not responded to therapy (P = 0.08). It was significantly higher 3 months after therapy (8.1 ± 9.1 mL) in responder compared with non-responder patients (−2.4 ± 7.1 mL, P = 0.02).
Conclusion: Thyroid volume changes either on palpation or by ultrasonography correlates well with clinical outcome of RAI therapy in hyperthyroidism, and can be used as a predictor of treatment efficacy.
Undesirable Effects after Remnant Ablation with Radioactive Iodine in Patients with Differentiated Thyroid Carcinoma: Our Experience
M. Agolti, M. Rettore
Nuclear Medicine, Clinica Modelo, San Martin 1238, Paraná, Argentina
Aim of the Study: Radioactive iodine therapy (RAI) is one of the most common treatments in differentiated thyroid cancer. RAI remnant ablation was demonstrated to be very useful in diminishing recurrence and mortality in high-risk patients; thus, we decided to register undesirable effects of this treatment referred to salivary glands, eyes, nauseas or vomiting and cystitis between our patients.
Materials and Methods: Seventy patients who had total thyroidectomy prepared with levothyroxine withdrawal and received ablative doses were included in the study. The doses administered were between 100 and 150 mCi. Symptoms were investigated 12 months after ablation through a questionnaire. We investigated the acute undesirable effects as follows: 1 - minor discomfort and swelling of the parotid and submandibular glands; 2 - nauseas or vomiting; 3 - mucositis oral; 4 - dyspnea or stridor; 5 - discomfort or swelling of the thyroid bed; 6 - vocal cord paralysis and chronic undesirable effects; 7 - xerostomia; 8 - alterations in taste; 9 - dry eyes; 10 - excessive tearing; 11 - pseudo sialolithiasis. Between the high doses, we had seven patients who had this as a second dose.
Results: The most common acute undesirable effects were minor discomfort and swelling of the salivary glands and nausea (vomiting in only one patient), found in 17 patients (24%), followed by cervical edema in nine patients (13%). Seven patients complained of had discomfort, different from the post-surgical in the thyroid bed, and seven referred symptoms related to actinic cystitis (10%). With regard to the chronic undesirable effects, we found an alteration in taste in 35 patients (50%) and xerostomia in 29 patients (41%). Twelve patients referred to pseudosialolithiasis (17%), 11 to excessive tearing (16%) and nine patients had dry eyes (13%).
Conclusion: As regards acute undesirable effects, nausea was more common than expected, as also actinic cystitis, although with good preparation. Taking into consideration the chronic undesirable effects related to salivary glands, these were more common than expected and were more common than that reported in the literature, although the literature refers to preparation with recombinant human thyroid stimulating hormone. Pseudosialolithiasis was much more common than that reported in the literature, and it always appeared at least 1 month after the dose. None of the patients referred persistence of symptoms when they were interrogated. The patients who received a second dose said that the undesirable effects were worse at the second dose.
Experimental Study of Targeting Glioma with 131 I-CH12 McAb
P. Li, L. Wang
Department of Nuclear Medicine, Rui Jin Hospital, Rui Jin 2 nd Road, 197#, Shanghai, China
Aim of the Study: Radioimmunotherapy has a remarkable effect on tumor therapy and plays an important role in the clinical treatment of tumors. In the recent 20 years, it has become one of the key methods in tumor therapy and has shown its advantage in nuclear therapy. Epidermal growth factor receptor (EGFR) vIII is the most frequently occurring EGFR variant that can promote tumor cell growth. In this experimental study, an anti- EGFR variant III monoclonal antibody that was developed in our laboratory was labeled by 131 I and used to treat glioma. This study aimed to study the treatment effect of 131 I-CH12 to glioma in tumor cells and tumor bearing nude mice.
Materials and Methods: The antibody CH12 was labeled with 131 I by the Iodogen method. Immunofluorescence and FACS analysis were used to detect the binding ability of CH12 with U87-EGFRvIII cell after labeling 131 I. CCK-8 assay were performed to evaluate the effect of 131 I-CH12 effect on glioma cells in the different test groups. Tumor xenograft models were established with U87MG-EGFRvIII cell line and the inhibitory rate of tumor growth was calculated and tumor apoptosis was observed by hematoxylin and eosin staining.
Results: The labeling efficiency and radiochemical purity of 131 I-CH12 were 51.74 ± 4.19% and 97.94 ± 2.37%, respectively. The binding ability of CH12 with the U87MG-EGFRvIII cell was not reduced after labeling with 131 I. The expression rate in the group of 131 I-CH12 was 78.75%, similar to the group of CH12 (79.83%). 131 I-CH12 can inhibit the proliferation of U87MG-EGFRvIII cells in vitro and tumor growth in vivo.
Conclusion: 131 I-CH12 has demonstrated to be a promising radioimmunotherapy agent to treat gliomas.
Expansion of Radionuclide Therapy in a Developing Country: Experience of Bangladesh
Nuclear Medicine, National Institute of Nuclear Medicine and Allied Sciences, Block-D, 7 th Floor, BSMMU, Shahbagh, Dhaka, Bangladesh
Abstract: The history of radionuclide in medical therapy is quite long. Starting from 131 I, many new radionuclides have been added in the list of theragnostics. Some of them are being used routinely with good results. In comparison with the last few decades, the share of radionuclide therapy in nuclear medicine is increasing fast in the recent years. However, the scenario is not the same in all parts of the world. Expansion of radionuclide therapy in developing countries is still very slow. Herein, our experience of a developing country like Bangladesh is described. Bangladesh is a small country in the south-east Asian region with a large population of about 150 million. The history of nuclear medicine in Bangladesh is quite old. The first nuclear medicine center was established in 1962. Since then, the number of nuclear medicine centers have increased to more than 20. The country's first PET center was established in 2010 with a cyclotron facility. Now, about 500,000 people get nuclear medicine services per year, but this is mainly diagnostic services. The theragnostic service is still very small, and is mainly limited to 131 I therapy for differentiated thyroid cancer and thyrotoxicosis patients. At present, about 1000s of patients get I-131 therapy per year. However, of the 20 centers, the therapy is mainly performed by one institute located in the Medical University Hospital in Dhaka. Besides 131 I therapy, 90 Sr is routinely used for the prevention of pterygium after surgery. Previously, 32 P was used for polycythemia vera but, for the last few years, this is not available here. The main bulk of isotopes are imported from abroad, and newer radiopharmaceuticals like 153 Sm, 89 Sr, 186 Re, 90 Y, MIBG or somatostatin analogs are very costly. The question of radioimmunotherapy is still very far. With the introduction of other imaging modalities like computed tomography, magnetic resonance imaging or ultrasound, the scope of radionuclide in the diagnostic field is gradually reducing. The developing countries are lagging behind in catching the present status of theragnostics. This is a great concern of sustaining nuclear medicine services in the developing world. The World Association of Radiopharmaceuticals and Molecular Therapy should take the matter in their notice and can play a role in homogeneous expansion of radionuclide therapy in all parts of the world.
Value of Baseline Thyroglobulin Level in Post-Thyroidectomy Patients with Differentiated Thyroid Cancer
F. A. H. Hussain, N. N. Nahar, F. A. Alam, M. H. Haque
Nuclear Medicine, National Institute of Nuclear Medicine and Allied Sciences, BSMMU Campus, Shahbag, Dhaka, Bangladesh
Aim of the Study: Thyroglobulin (Tg) is a well-established thyroid cancer tumor marker. The aim of this study was to evaluate the predictive value of the first serum Tg measurement (baseline Tg) after total thyroidectomy and before radioiodine ablation in differentiated thyroid carcinoma.
Materials and Methods: This retrospective study was performed on post-thyroidectomy patients with differentiated thyroid cancer presenting at the National Institute of Nuclear Medicine and Allied Sciences for iodine-131 therapy. A total of 212 consecutive patients were followed-up for 5 years (2007-2012). Data were collected including early post-operative pre-ablation Tg (ng/mL) values, post-therapeutic Tg levels, I-131 whole body scans on a regular basis and other related techniques, if necessary.
Results: According to the baseline Tg levels, patients were classified into four groups: 0-4, 4.1-10, 10.1-50 and >50. Higher levels of baseline Tg were observed in patients with a larger size of residual tissue (11.8%) and in more extensive disease at the time of presentation, such as neck lymph node metastases (20%) and distant (bone, lung) metastases (5.6%). Fifteen (of 212) patients (7%) had a baseline Tg level >50. Patients (15%) with higher levels of Tg required multiple doses for remission of either persistent or recurrent disease. Lower Tg levels (<4) were associated with negligible residual thyroid tissue or a lesser number of metastases. Most of the patients with lower levels of baseline Tg (<2) were found to be in a disease-free state at the last follow-up.
Conclusion: In well-differentiated thyroid cancer patients, the post-thyroidectomy baseline Tg level (0-4 ng/mL) is associated with a low probability of metastases, persistence of disease and recurrence; thus, it is a good predictor in disease staging for proper management.
The Most Common Complaints of Thyroid Cancer Patients Post-Thyroidectomy and Radioiodine Therapy: A Preliminary Report
S. Shafiei, N. K. Ayati, S. R. Zakavi, H. Sadra, S. Zare Namdar
Nuclear Medicine Research Center Ghaem Hospital, Mashhad University of Medical Science, Ahmad-Abad, Mashhad, Iran
Aim of the Study: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy in the world, and includes approximately 1% of all cancers. Most of the thyroid cancer patients are middle aged and have a long survival. Therefore, the quality of life in the remainder of their life is an important factor that needs great attention. If we can discover the most common complaints, we would be able to reduce their incidence and, consequently, prepare a better life for DTC patients. Additionally, the classic treatment protocol of DTC includes surgery, radioactive iodine therapy and, in some cases, external beam radiotherapy. Each of these treatment modalities has its special complications that can result in different complaints of the patients.
Materials and Methods : We evaluated 300 DTC patients after thyroidectomy and iodine therapy who had been followed-up for at least 1 year. We asked about their complaints personally in each visit and recorded them in their document folders. Then, we adopted all the patients' problems from their document folders and analyzed them with SPSS V.11.9.
Results: Three hundred DTC patients (272 female and 28 male) with a mean age of 40.9 ± 16.4 years were included in our study. The most common complaints of the DTC patients were generalized bone pain, neck discomfort, fatigue and weakness, dyspnea, palpitation, parenthesis of the limbs, nervousness, headache, numbness of the limbs, xerostomia, edema, tremor and hoarseness.
Conclusion: Generalized bone pain appeared in the older patients, and could be due to degenerative diseases, bone metastasis or as a result of hypothyroidism. The second most common complaint was neck pain that originated from thyroid surgery. Weakness and fatigue can be due to hypocalcaemia, hypothyroidism or poor energy diet in our patients. This is the first research about the most common complaints in DTC patients. We are going to define the relationship between these complaints and other factors such as gender, age, treatment protocol, serum TSH level and levothyroxine dosage.
Accuracy Study of Sentinel Node Biopsy by 99m Tc Phytate in Patients with Non-Small Cell Lung Carcinoma: A Preliminary Report
S. Shafiei, R. Bagheri, R. Sadeghi, A. H. Jafarian
Nuclear Medicine Research Center Ghaem Hospital, Mashhad University of Medical Science, Ahmad-abad, Mashhad, Iran
Aim of the Study: Lymph node metastases are the most significant prognostic factors in localized non-small cell lung cancer (NSCLC). Identification of the first nodal drainage site (sentinel node) may improve the detection of the metastatic nodes. Moreover, extended surgeries such as lobectomy or pneumonectomy with lymph node dissection (hilar and mediastinal) are gaining more acceptance for the treatment of this malignancy. Sentinel node biopsy can be an alternative approach in this regard to perform surgeries less invasively. We evaluated the accuracy of sentinel node mapping in 15 patients with NSCLC using intra-operative radiotracer techniques.
Materials and Methods: Immediately after thoracotomy and before mobilizing the tumor, a peritumoral injection of 2 mCi/0.4 mL Tc-99m-phytate was performed in four corners of the tumor. After mobilization of the tumoral tissues, the sentinel nodes were searched for in the hilar and mediastinal areas using a hand-held gamma probe. Any lymph node with an in vivo count twice that of the background was considered as a sentinel node and removed and sent for frozen section evaluation. All the dissected nodes were evaluated by step sectioning and hematoxylin and eosin staining (H and E).
Results: Fifteen patients (10 male and five female) were included in the study, with an age of 62.3 ± 9.25 years. At least one sentinel node could be identified in all patients (detection rate of 100%). The mean number of sentinel nodes per patient was 2.3 ± 1.3 (median of three nodes per patient). All the detected sentinel nodes were hot and no cold sentinel node was harvested. A false-negative rate of 0% (0/15) was noted in the study. Frozen section results showed 100% concordance with the H and E results. To the extent of our knowledge, our study is the only study thus far that evaluated frozen section accuracy in sentinel node biopsy of lung cancer.
Conclusion: Sentinel node mapping can be considered as a feasible and accurate method for lymph node staging (detection rate of 100% and false-negative rate of 0%) and NSCLC treatment.
Characteristics of Differentiated Thyroid Carcinoma Patients with Low Serum Thyroglobulin: Off Level but Positive Post-Therapy 131 I -WBS in the First Six Months Follow-Up
Nuclear Medicine, Hasan Sadikin Hospital, Jl Pasir Kaliki no 192, Bandung, Indonesia
Background: 131 I-WBS and serum Tg are important tools in the detection of recurrent or persistent differentiated thyroid carcinoma. Based on prior studies, 131 I WBS may detect a new lesion in up to 50% of the patients with differentiated thyroid cancer (DTC) post-ablation. Tg is a tumor marker for DTC - detectable or elevated serum Tg is associated with persistent diseases whereas undetectable Tg is correlated with complete remission, provided that anti-Tg antibodies are not present. Prior studies have found some discrepancies between the serum thyroglobulin finding and 131 I-WBS.
Materials and Methods: This was a retrospective study in our department, where 70 subjects with DTC post-total thyroidectomy or near-total thyroidectomy between 2011 until 2013 were followed by 131 I ablation. All subjects were undergoing first control 131 I-WBS and serum thyroglobulin measurement at 6-12 months post-ablation. We found that five subjects were Tg serum negative and diagnostic 131I WBS positive, whereas four of these five subjects also had a positive 131 I WBS post-therapy. Serum Tg negative was defined as a Tg of <3 ng/mL with TgAb negative under TSH stimulation.
Results: Four DTC subjects had papillary thyroid carcinoma, and three of these subjects were positive for 131 I WBS in the lymph node, lung and thyroid bed. The other sites for positive uptake were in the thyroid bed and in the lung. One patient with thyroid follicular carcinoma had a positive 131 I-dWBS in the thyroid bed.
Conclusion: Very low Tg level can be associated with papillary histologic characteristics, small size of tumor and micrometastasis. The follow-up of thyroid cancer should not based on Tg determination, even after suppressive therapy withdrawal. The combination of 131 I WBS and serum Tg value is superior than that of Tg alone and the early detection of persistent or recurrent DTC.
Remnant Ablation using 1 GBq (30 mCi) I-131 in High-Risk Differentiated Thyroid Carcinoma Patients
S. Fithriany, Basuki Hidayat, Budi Darmawan, A. Hussein, S. Kartamihardja, Johan S. Masjhur
Departments of Nuclear Medicine, and Molecular Imaging School of Medicine Universitas Padjadjaran, Dr. Hasan Sadikin Hospital, Bandung Indonesia
Aim of the Study: Many guidelines or consensus were recommended for using radioiodine ablation after total thyroidectomy for high-risk differentiated thyroid carcinoma (DTC) to ablate the remnant thyroid. However, because of many reasons, not all after-total thyroidectomy high-risk DTC patients can receive high doses of RAI. Alternatively, a low dose of NaI-131 (1 GBq to 30 mCi) was given to that group of patients. The aim of this report was to describe the outcome of 30 mCi NaI-131 to ablated remnant thyroid tissue in high-risk DTC patients.
Materials and Methods: The data were collected from the medical records in the years 2011-2013. We analyzed those medical records (2011-2013) that had at least 6 months of follow-up after radioiodine ablation. Patients were considered as high risk of DTC according to the AMES and/or histopathological findings. The post total thyroidectomy thyroglobulin serum level was classified in two groups: <6 ng/dL and >6 ng/dL. Positive response was defined as withdrawal thyroid hormone thyroglobulin serum level (Tg-off) <2 ng/dL and negative antithyroglobulin antibody.
Results: There were 70 patients of DTC who received RAI at that time of the data collection period. Twenty-seven of 70 patients received 30 mCi NaI-131. Seven of the 27 patients (four female and three male; age: 22-70 years) were at a high risk of DTC, with histopathological results showing papillary thyroid carcinoma. The high-risk criteria were multifocal in two patients, with evidence of lymph node metastases in two patients, age 51 years in one patient, evidence of distant metastasis (lung) in one patient and evidence of distant metastases (vertebrae, pelvic) and lymph node metastasis in one patient. The thyroglobulin serum level before ablation was in the range of 1.9 to >250 ng/dL. Two patients had a post-total thyroidectomy thyroglobulin serum level <6 ng/ dL (1.9 ng/dL each). Positive response was found in two patients who had a Tg-off <6 ng/dL; high-risk component: age >45 years in one patient and lymph node metastases in the other patient.
Conclusion: Low doses (30 mCi) of NaI-131 for RAI in high-risk DTC was not promising. However, good response could be expected in high-risk DTC patients who had a post-total thyroidectomy thyroglobulin serum level <2 ng/dL.
Clinical Significance of Thyroglobulin Antibody Pattern in Patients with Differentiated Thyroid Carcinoma
F. Hutomo, I. D. Mulyanto, H. Kartamihardja
Nuclear Medicine RS, Hasan Sadikin, Pasirkaliki no 192, Bandung, Indonesia
Aim of the Study: 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 a positive TgAb after remnant ablation were included in the study. The serum TgAb level was measured in levothyroxine withdrawal at post-operation and post-ablation. All patients had received a minimum of two times of radioiodine therapy. Residual and remission of disease were qualitatively and semiquantitatively analyzed from two consecutive post-radioiodine therapy whole body scans (WBSs).
Results: Thirty-two DTC patients with positive TgAb were classified in the increasing (13 of 32) and decreasing (19 of 32) groups. From the increasing TgAb group, nine patients showed a positive TgAb 6 months post-remnant ablation, while the other four patients showed a positive TgAb >1 year after remnant ablation. Only one patient of the increasing TgAb group showed remission, while the rest of the patients showed residual disease with more lesion number or increased radioactive uptake. Patients of the 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 a high serum Tg level.
Conclusion: The pattern of TgAb level might depict disease status in patients with DTC, especially in those with a low Tg level.
Role of Dual Point 18 F-FDG PET/CT Imaging in the Assessment of Micrometastases in Breast Cancer Patients
M. K. Srivastava, S. Simon, P. Venkat, M. Indirani
Department of Nuclear Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanavanthri Nagar, Puducherry, India
Aim of the Study: Presence of micrometastases has been considered as a drawback in 18 F-FDG PET/CT imaging. In this prospective study, we used dual time point PET/CT imaging to study the axillary nodes in confirmed breast cancer cases. The results were correlated with the frozen section after sentinel node biopsy and final histopathology by immunohistochemistry (IHC).
Materials and Methods: Thirty-five biopsy-proven breast cancer patients, referred by an oncologist, were evaluated in an 18 F-FDG PET/CT study. Patients underwent FDG imaging by the usual protocol. Another delayed imaging was performed after 2 hours of the injection. The % change in SUVmax (∆%SUV max) was calculated for the axillary nodes. Patients underwent a sentinel node procedure, where the nodes were correlated by PET/CT images. All nodes were separately labeled and sent for frozen section and for final histopathology by IHC.
Results: A total of 55 nodes were examined as sentinel node in 35 patients. Thirty-three nodes were positive for metastases in the frozen section while the remaining 22 nodes were negative for metastases on frozen section. Of the negative nodes, eight nodes showed micrometastases in the final histopathology by IHC. The ∆% SUV max of the nodes with micrometastases was 24.46 ± 16.30, while it was 7.07 ± 17.80 in the other nodes. This difference in ∆% SUV max between the nodes with micrometastases and those without micrometastases was significant (P <0.05). However, when the absolute SUV max was considered, the SUV max of the negative sentinel nodes with the presence of micrometastases was 2.05 ± 1.01 and that of the rest of the negative nodes without micrometastases was 3.11 ± 1.94. The SUV max of the negative nodes without micrometastases was higher, but it was not statistically significant (P = 0.10795).
Conclusion: Although the SUV max of the sentinel node negative for micrometastases was higher than for that for those with micrometastases, the ∆% SUV max correctly identified the nodes that had micrometastases on final IHC histopathology.
Radionuclide Therapy Modalities: Local Experience in the Nuclear Medicine Department of MRCCC - SHS
I. D. Mulyanto, R. Yudistiro, H. Budiawan, D. Nariman, E. Purnomo, B. Hidayat
Nuclear Medicine, MRCCC Siloam Hospital Semanggi, Jalan Garnisun Kav. 2-3, Jakarta, Indonesia
The Mochtar Riyadi Comprehensive Cancer Centre Siloam Hospital Semanggi (MRCCC-SHS) is a relatively new private cancer center located in the heart of Jakarta-Indonesia. One of its excellences is its integrated nuclear medicine department, which is equipped with PET/CT, SPECT, 18/9 IBA cyclotron and six radiation isolation rooms for the purpose of radionuclide therapy services. We performed a descriptive retrospective study of radionuclide therapy performed in our nuclear medicine department. Since it was opened in April 2011, until now, there have been 67 radionuclide therapy services performed, including radioiodine treatment for benign and malignant thyroid disease, Sm-153 EDTMP for bone pain palliative therapy, I-131 MIBG for neuroblastoma and P-32 for keloid and hypertrophic scar. Radioiodine therapy divided was into benign thyroid disease in 21 cases and malignant thyroid disease in 37 cases. As many as 13 of the 21 radioiodine therapies for benign thyroid disease were hyperthyroidism cases with an I-131 dose range of 7-10 mCi, of age 22-54 years and of frequency one to three-times to achieve the outcome. The malignant thyroid disease cases received radioiodine therapy including papillary thyroid carcinoma in 30 of 37 cases, with a dose range of 30-200 mCi. There were three cases of metastases bone disease who received a dose of 1 mCi/ kg BW Sm-153 EDTMP, including the lung, prostate and thyroid cancer cases. One pediatric (8 years old) neuroblastoma patient received a dose of 100 mCi I-131 MIBG after the I-131 MIBG diagnostic scan. Also, three patients with keloid received P-32 therapy with a dose of 50-100 μCi per lesion. We are developing currently existing radionuclide therapy modalities and more targeted radionuclide therapy services in the future such as radioimmunotherapy, radioembolization and PRRT.
Case Study: First Experience in I-131 MIBG Palliative Therapy for Refractory Neuroblastoma Patients
R. Yudistiro, D. Garniasih
Nuclear Medicine, MRCCC Siloam Hospital Semanggi, Jakarta, Indonesia
We reported our first experience of I-131 MIBG palliative therapy for refractory neuroblastoma in the Nuclear Medicine Department of the MRCCC Siloam Hospital Semanggi. A 7-year-old boy was diagnosed with neuroblastoma based on the histopathological result from the biopsied tumor in the abdomen. The patient had abdominal pain 2 weeks before hospitalization. The abdominal ultrasound showed multiple mixed echoic lesions in the right lobe of the liver and multiple lesions in the left paralumbar hypochondral region on the anterior side of the left renal and also on the posterior side of the urinary bladder, suspicious for neuroendocrine tumor. For treatment of the abdominal pain, an analgesic intravenous and topical was given to the patient three times a week. The patient underwent chemotherapy for nine cycles with three different regimens, but no positive response for abdominal pain was noted. An FDG PET scan showed multiple hypermetabolic nodules in the liver and hypermetabolic lymphadenopathies in the mediastinal, abdominal and pelvic muscles with pleural effusion and right lung collapse. The pediatrician referred the patient to the nuclear medicine department for I-131 MIBG therapy with an aim to reduce the abdominal pain. I-131 MIBG diagnostic scanning was performed to confirm the neuroblastoma lesion and also for pre-therapy scanning for I-131 MIBG therapy. I-131 MIBG with an activity of 100 mCi was injected intravenously through the infusion fluid. The patient was isolated for 5 days until the radiation exposure reached a safe limit for the environment. After the administration of I-131 MIBG, the abdominal pain decreased and the patient felt comfortable for 2 weeks. Analgesics could be reduced to once a week. Unfortunately, after 2 weeks of the I-131 MIBG palliative therapy, the patient started to feel abdominal pain again and analgesics were readministered three times a week. After 2 months post I-131 MIBG palliative therapy, the patient had vena cava superior syndrome due to the compressing effect from the mediastinal mass. The patient had shortness of breath and the general condition was decreased. External beam radiation was given 10 times to the patient, but this did not relieve the shortness of breath until the patient died. Neuroblastoma is a common solid extracranial malignancy in pediatric patients. Treatments for neuroblastoma include surgery, chemotherapy or radiotherapy. Some patients are refractory to chemotherapy and have continuous pain due to the effect of the tumor. This pain often does not respond well with conventional analgesics. Metaiodobenzylguanidine (MIBG) is an analog substance from norepinephrine that is expressed by more than 90% of the neuroblastoma cells. MIBG labeled with I-131 will be taken up by the neuroblastoma cell. From this experience, we learned about the I-131 MIBG procedure as palliative therapy in neuroblastoma. In our opinion, I-131 MIBG may be useful as a palliative therapy in refractory neuroblastoma patients.
The Benefits of Adjuvant 131 I Therapy for Differentiated Thyroid Carcinoma with Elevated Thyroglobulin and Negative 131 I Whole Body Scan
L. Herawati Diah, B. Hidayat, B. Darmawan, A. H. Kartamihardja
Department of Nuclear Medicine and Molecular Imaging, School of Medicine Universitas Padjadjaran, Dr Hasan Sadikin Hospital, Bandung Indonesia
Aim of the Study: Management of differentiated thyroid carcinoma with elevated serum thyroglobulin level and negative 131 I whole body scan (TENIS) is still controversial. One of the treatment options was to treat the patients with multiple high doses of 131 I. The aim of this paper was to share our local experience in handling TENIS cases with high-dose 131 I.
Materials and Methods: Data were obtained from the medical records of patients between 2011 and 2013. The analyzed medical records were to be complete and were to contain a minimum of a 6-month period post-adjuvant therapy follow-up. TENIS cases were defined as an elevated serum thyroglobulin level above the cut-off point of 3 ng/mL under TSH stimulation after cessation of L-thyroxine for 4 weeks (called Tg-off), but with a negative post-therapeutic 131 I whole body scan. In TENIS cases, a positive therapy response was considered if there was a decreased serum Tg-off level with a negative or persistent/decreasing antithyroglobulin antibodies (ATAs) at 6 months post-ablation follow-up.
Results: There were 70 patients of differentiated thyroid carcinoma receiving 131 I therapy. Seven of the 70 patients were considered as TENIS cases, but only five of these seven patients had complete medical records. Those patients received a cumulative dose of 250-580 mCi. Laboratory findings showed a negative ATA in three patients and a positive ATA in the remaining four patients. One patient showed a decreased serum Tg-off level with a negative ATA. Two patients showed a decreased serum Tg-off level but a positive ATA, wherein the trend was to decline. At 6 months post-therapy follow-up, there were three patients with a positive therapy response.
Conclusion: Adjuvant 131 I therapy in TENIS cases might be still beneficial, while the positive therapy response was defined as a decreased serum Tg-off level with negative ATA or with a positive ATA, wherein the trend was to decline.
In vivo SPECT Imaging and Biological Evaluation of 198,199 Au-Labeled Graphene Oxide Nanoflakes as Therapeutic Agents
Y. Fazaeli, O. Akhavan, R. Rahighi, M. Aboudzadeh, E. Karimi, H. Afarideh
Department of Nuclear Medicine, Agricultural, Medical and Industrial Research School (AMIRS), Karaj, Iran
Nanoflakes of graphene have been given much attention in the recent years due to the facility of a wide variety of different functionalizations as outstanding nanoactive agents for various fascinating biomedical purposes. The superior effective surface area (2.63 m 2 /mg), high thermal conductivity (5000 W/mK), enormous NIR absorbance, favorable tumor passive targeting and minimum side-effects are some of the unique physicochemical properties of this promising nanomaterial. The goal of this study was to utilize nano-graphene for tumor targeting in rats bearing fibrosarcoma tumor and evaluate the pharmacokinetics and tumor-targeting potency through single-photon emission tomography (SPECT) imaging using 198 Au and 199 Au as the radiolabel. Nano-graphene oxide (GO) sheets functionalized with 3-aminopropyl-trimethoxy silane were treated with radioactive gold in the form of tetrachloroauric acid (H[ 198,199 -Au] Cl 4 ) to form the covalently bonded amino gold complex. The final complex was then utilized via tail vein injection. The animal tests revealed a high uptake of 198,199 AuCl 3 GO in the tumor. The stability of the compound was confirmed in human serum.
Bone Lesion Score: A Predictor of Success of Radionuclide Therapy in Skeletal Metastasis
G. Jameel, S. Saeed, S. Butt, S. Fatima
Nuclear Medicine Department, Nuclear Medicine, Oncology and Radiotherpy Institute, Islamabad, Pakistan
Aim of the Study: To device a method of quantitative assessment of the extent of skeletal metastasis and to predict the efficacy of radionuclide therapy for bone pain palliation on the basis of this scoring system.
Materials and Methods: Twenty patients with stage IV breast carcinoma and prostate carcinoma, and diagnosed to have skeletal metastasis, were enrolled in this study. A Tc-99m MDP bone scan was performed in every case. Bone lesion score was calculated after performing the Tc-99m MDP bone scan according to the bone lesion scoring system devised for the assessment. The number of corresponding painful sites was counted by clinical history and examination. Every patient was injected with 2600 MBq Lu-EDTMP after 1 week of the initial bone scan and initial blood cell counts. Follow-up of patients was performed every week for blood counts to monitor the marrow toxicity and pain response, which were monitored with the help of a universal visual analogue scale (grade 0-grade 10). A reduction in the number of painful sites was noted in every case.
Results: The follow-up of patients after 2600 MBq Lu-EDTMP showed a better pain palliative response with an initial bone lesion score of below 8. With a bone lesion score of 8-10, the pain score reduction can be graded as minimal. The pain palliation was negligible in cases with a bone lesion score of 11-15.
Conclusion: Bone lesion score can be considered as a predictor and an indicator of the success of radionuclide pain palliative therapy with Lu-EDTMP. The patients with a score of more than 10, indicating extensive skeletal involvement, should not be considered as candidates for radionuclide therapy as the risk of bone marrow suppression outweighs the palliative benefits that are statistically limited.
Patient Characteristics and Outcomes of Radioiodine Therapy in Differentiated Thyroid Cancer with Ineffective TSH-Stimulation: A Case Series
A. R. Dewi, B. Hidayat, B. Darmawan, A. H. S. Kartamihardja
Department of Nuclear Medicine and Molecular Imaging, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia
Aim of the Study: Adjuvant radioiodine therapy in differentiated thyroid cancer (DTC) is known to be effective when given when the TSH level is >30 μIU/mL. This can be achieved by thyroid hormone withdrawal (THW) or administration of rhTSH, which is currently unavailable in our country. However, some of the patients fail to have a rise in their TSH level after THW. The aim of this study was to describe the patient characteristics and also the outcomes of radioiodine therapy in DTC patient with ineffective TSH stimulation.
Materials and Methods: Six DTC patients with pre-therapy TSH levels never exceeding 30 μIU/mL after a minimum of 4 weeks of THW were monitored and were retrospectively selected from a total of 829 patients receiving radioiodine therapy at the Department of Nuclear Medicine and Molecular Imaging, Dr. Hasan Sadikin Hospital, in the years 1996-2013. Patient characteristics data, such as age, histopathology, metastases and functional thyroid remnant, were collected. Pathologic uptake of I-131 was determined as uptake outside physiologic uptake (metastatic lesion). Patients were followed-up clinically by measuring TSH, thyroglobulin-off (Tg-off) and antithyroglobulin antibody (ATA). Response to therapy was defined as good response if there were a decreasing trend of serum Tg-off level and negative ATA or decreasing/stable ATA level.
Results: All patients, four with papillary thyroid carcinoma and two with follicular thyroid carcinoma, underwent total thyroidectomy and received cumulative doses of 60-700 mCi in two to seven cycles of therapy. Post-ablation I-131 whole body scan in all patients showed a large uptake on the thyroid bed and wide distant-metastatic lesions. Two patients showed a decreasing level of Tg-off; however, only one of them showed good response. Three patients had an increasing trend of Tg-off, while one patient was lost to follow-up.
Conclusion: Radioiodine therapy in DTC with ineffective TSH-stimulation was not promising. Good response may occur, particularly in patients with a decreased level of serum Tg-off and negative serum ATA, in the course of follow-up.
Nuclear Medicine: Ethical Issues in the Current Practices
S. Fatima, B. Shiekh, S. Butt, G. Jameel
Nuclear Medicine Department, Nuclear Medicine, Oncology and Radiotherapy Institute, Islamabad, Pakistan
Abstract: Recent advances in medicine have changed the horizon of diagnosis and treatment altogether. Nuclear Medicine being a technologically driven specialty has been one of the front runners for this change. With the introduction of new imaging technologies and novel therapeutic options, Nuclear Medicine faces many new ethical challenges because new treatment options and imaging modalities have a potential to be misused. Ethical principles have been traditionally considered as generic skills applicable to scientists and doctors, with only symbolic refinement at a particular specialty level. Specialist bodies across the world representing wide groups of practitioners frequently have subgroups dealing exclusively with ethical issues. However, specialties like Nuclear Medicine, with relatively smaller memberships, hardly have such provisions. Nuclear Medicine across the world is mostly being practiced according to the local set of radiation-related regulations and a separate code for Nuclear Medicine in addition to the general codes of conduct and practice for doctors. This paper will review the basic ethical concepts that are pertinent to the field of Nuclear Medicine and will discuss the ethical treatment of patients, colleagues, employers and the medical imaging profession as a whole. This paper will critically analyze the recent therapy and imaging-related publications in reputed Nuclear Medicine journals and analyze the commonly documented or undocumented ethical issues in the same. Another aim of this analysis is to explore the practice of evidence-based Nuclear Medicine within the ethical framework.
Value of Tl-201 Imaging in Predicting Therapeutic I-131 Uptake in Patients with Thyroglobulin-Positive but I-131 Scan-Negative Differentiated Thyroid Cancer
D. Tumapon, J. Obaldo
Nuclear Medicine Division, Philippine Heart Center, Quezon City, Philippines
Aim of the Study: Serum thyroglobulin assays and I-131 imaging are routinely employed for the assessment of functioning thyroid tissue remnants and metastases after surgery and radioiodine therapy. However, the sensitivity of I-131 is suboptimal, resulting in cases of positive thyroglobulin test but negative I-131 imaging. This has created a dilemma in the therapeutic management. Other radiopharmaceuticals, such as Tl-201 thallous chloride, offer better sensitivity than I-131 although it is not clear whether these contribute to the decision-making for subsequent I-131 therapy. This prospective cohort study aimed to determine whether Tl-201 imaging identifies thyroid tissues that will take up therapeutic I-131 and to help define its clinical utility in this subgroup of patients.
Materials and Methods: A total of 14 consecutive patients who underwent surgery for well-differentiated thyroid cancer, with elevated thyroglobulin (>10 ng/ mL) but negative pre-therapy (111 MBq) I-131 whole body scan (WBS), were enrolled in the study. WBSs were performed using 56-74 MBq of Tl-201. All patients subsequently had radioactive iodine ablation (3.7-7.4 GBq) 1-2 months after Tl-201 imaging. Post-therapy WBS was performed 4-7 days thereafter. Concordance of the Tl-201 WBS with the post-therapy was determined by consensus of two nuclear medicine experts.
Results: Of the 14 patients, 10 had positive Tl-201 imaging, of which only two had positive post-therapy WBS. Thallium-201 scanning showed a fairly high sensitivity (71%) in demonstrating thyroid remnants using a thyroglobulin level of >10 ng/mL in the setting of a negative pre-therapy scan. However, positive Tl-201 scan is a poor predictor (positive predictive value of 20%) of subsequent uptake of therapeutic I-131, as shown in the post-therapy scan.
C onclusion: Thallium-201 uptake correlates poorly with therapeutic I-131 uptake in thyroglobulin-positive but I-131- scan-negative differentiated thyroid cancer patients. The results of this study suggest that the presence of thyroid tissue remnants and metastases on Tl-201 imaging is an appropriate basis for the decision to proceed with I-131 therapy. The role of Tl-201 scanning in this subset of patients may be limited for identifying the lesions for surgery or external beam radiation therapy.
PNRI Pioneering Local Production of Molybdenum-99/Technetium-99m (Mo-99/Tc-99m) Generators for Nuclear Medicine Centers in the Philippines
A. Bulos, A. Dela Rosa, M. D. P. Latido, R. Mascarinas, M. T. Borras
Nuclear Services, Philippine Nuclear Research Institute, Quezon City, Philippines
Abstract: Since the establishment of the country's first nuclear medicine center in the 1950s, one challenge to nuclear molecular imaging and diagnostic procedures that still holds true up to the present is the lack of the domestic production of medical radioisotopes and radiopharmaceuticals. All of the medical radioisotopes and radiopharmaceuticals demands in the country were met through importation. Nuclear medicine has become an integral part of the country's health care institutions as evidenced by the establishment of various nuclear medicine centers in the provinces. Nuclear medical procedures are common yet are not always an option due to the high cost of procurement of radioisotopes and radiopharmaceuticals. The Philippine Nuclear Research Institute (PNRI), through the assistance of the International Atomic Energy Agency (IAEA) and the Grants-in-Aid Program of the Department of Science and Technology (DOST-GIA), addresses the issue of radioisotope production by establishing a production facility for Mo-99/Tc-99m generators (or Tc-99m generators for short), the main source of Tc-99m, still the most frequently used radioisotope in nuclear medicine. The establishment of the Technetium-99m Generator Production Facility is under the institute's Nuclear Services Division's Isotope Techniques Section. It is a 3-year project that started in 2011 with the goal of providing the generators to about 35 hospitals in the country and making organ scintigraphy tests affordable and more accessible to the Filipino people. The Generator Facility is located in the PNRI premises housing more than 400 square meters of floor space of the state of the art facilities solely for the production and quality control of Tc-99m generators. The facility is compliant with the local and international standards on radiation safety and Good Manufacturing Practices. It is designed and built by Isotope Technologies Dresden (ITD) of Germany and PNRI. Among the initiatives being undertaken to prepare the facility for eventual operation were:
• Securing the authorization to use radioactive material from the institute's regulatory office
• Securing the license to operate from the Food and Drug Administration (Philippine FDA)
• Provision of other core and essential fixtures, materials and equipment
• Hiring of qualified personnel to man the facility and capability building through trainings, seminars and scientific visits, both local and abroad
• Development and improvement of the production and quality control protocols for the generator and eluate
• Establishing logistics schemes for distribution to hospitals.
Two test production runs have been conducted since the completion of its core facilities in 2012. The first test was conducted by an IAEA consultant and the ITD. The second test was conducted by the trained PNRI personnel who were responsible for the operation and maintenance of the facility. Both pilot runs were successful in meeting the international standards for Tc-99m for medical use, namely Mo-99 breakthrough, radionuclide purity and radiochemical purity, among other tests. At present, the PNRI Tc-99m Generator Production Facility is complete. While awaiting the licenses from the authorities for commercial operation, the marketing and distribution scheme is being established.
Development of a Novel Porphyrin Complex as an imaging agent: [ 67 Ga]-3,4 Dimethoxylated Porphyrin
Y. Fazaeli, A. Jalilian, A. Paknafas, S. Feizi, M. Kamalidehghan, A. Rahiminezhad
Nuclear Medicine Department, Agricultural, Medical and Industrial Research School (AMIRS), Karaj, Iran
Abstract: Radiolabeled porphyrins are potential tumor avid radiopharmaceuticals because of their impersonation in the human body, ability to complex various radionuclides, water solubility, low toxicity, etc., In this work, a radiogallium porphyrin complex has been developed. [ 67 Ga]- labeled 5,10,15,20-tetrakis (3,4-dimethoxyphenyl) porphyrin ([ 67 Ga]-TDMPP) was prepared using freshly prepared [ 67 Ga] GaCl 3 and 5,10,15,20-tetrakis (3,4-dimethoxyphenyl) porphyrin (H2TDMPP) for 60 min at 100°C. Stability of the complex was checked in the final formulation and human serum for 24 h, followed by biodistribution and imaging studies in wild type rats up to 24 h. The radiocomplex was obtained with a radiochemical purity >99% (ITLC) and >98% (HPLC) and specific activity of 12-15 GBq/mmol. The partition coefficient was determined (log P = 1.63). A detailed comparative pharmacokinetic study was performed for 67 Ga cation and [ 67 Ga]-TDMPP. The complex is mostly washed out from the circulation through the kidneys. Myocardial uptake was significantly observed by SPECT and biodistribution studies. Knee and shoulder joints demonstrated significant activity uptake at 2 h post-injection. Higher water solubility of the complex due to the ionic nature of the complex is an advantage for rapid wash-out of the complex from the system; the complex has significant joint uptake compared with other radiolabeled porphyrins, the mechanisms of which are explained.
Nanopurification and Quality Control of [ 64 Cu] CuC l2 by amino functionalized Fe 3 O 4 magnetic nano-particles
Yousef Fazaeli, Ali Sattari
Department of Nuclear Medicine, Agricultural, Medical and Industrial Research School (AMIRS), Karaj, Iran
In this work, Fe 3 O 4 nano-particles were synthesized and their formation was established by X-ray powder diffraction and scanning electron microscopy. Single-point BET analysis showed a 390 m 2 /g surface area for the Fe 3 O 4 nano-particles. Modification of the Fe 3 O 4 nano-particles' surface with (3-Aminopropyl) trimethoxysilane was carried out through the direct method of functionalization in toluene. In this procedure, the hydroxyl groups on the surface of the Fe 3 O 4 bind to the silyl groups by means of hydrolysis of the methoxy groups. The CHN analysis shows that the total loading of the amine groups was about 0.52 mmol/g of functionalized oxide. This nano-oxide was then experienced in purification of the prepared [ 64 Cu] CuC l2 solution. The solution was transferred to functionalized Fe 3 O 4 nano-resins to remove the trace amounts of zinc that remained in the solution. In this step, the 64 Cu ions remain on the nano-resin. In order to elute the copper-64 ions, the nano-resin was eluted using 50 mL of 2 N HCl and highly pure [ 64 Cu] CuC l2 was achieved.
Radioiodine Therapy in Differentiated Thyroid Carcinoma: Long-Term Follow-up
M. Hoque, F. A. Hussain, F. Alam, A. K. Sarker
Nuclear Medicine Department, Institute of Nuclear Medicine and Allied Sciences, Dhaka, Bangladesh
Aim of the Study: Accurate surveillance for possible recurrence in apparently disease-free patients after radioiodine therapy in differentiated thyroid carcinoma is a major goal of long-term follow-up. Also, monitoring of thyroxine suppression or replacement therapy to avoid under-replacement or over dose is a second goal of long-term follow-up. The aim of this retrospective study was to evaluate the outcome and impact of the long-term (12-32 years) follow-up of patients with differentiated thyroid carcinoma treated with radioiodine.
Materials and Methods: From a total of 2851 post-thyroidectomy patients with differentiated thyroid carcinoma receiving radioiodine therapy at the Institute of Nuclear Medicine and Ultrasound, Dhaka (between 1980 and 2012), a retrospective study was performed on 443 patients treated during the period from 1980 to 2000 (in the previous years, comparatively smaller numbers of patients presented at the institute for radioiodine therapy than those presenting in the recent years). The medical records of these patients were analyzed in December 2012 in order to evaluate the follow-up workup for a prolonged period of time (12-32 years). Evaluation of the case files included annual physical examination, serum Tg measurement on replacement L-T4, neck ultrasonography and whole body scan, where necessary. The period of follow-ups, date of last visit and existing status of each patient were recorded.
Results: Of the 443 patients, 79.45% had papillary thyroid carcinoma and the rest had follicular type carcinoma. A total of 30 patients (6.77%) were lost to follow-up after the first dose of therapy. About 15.12% (67 patient), 4.96% (22 patients), 5.64% (25 patients) and 5.64% (25 patients) had follow-up workup for 1, 2, 3 and 5 years, respectively. About 3.6% and 5.2% patients showed up for a long-term follow-up of 10 and 15 years, respectively. A small number of patients (five and seven patients) had 20 and 25 years of follow-up. Only one patient had a regular follow-up for 28 years. A total of nine patients (2.03%) were recorded in our case files as expired. A good number of patients (66 patients) required multiple doses (three to eight patients; each dose ranging from 100 to 250 mci) and two patients received nine and 10 doses (a total of 1890 and 2062 mCi) of radioiodine to treat the persistence of disease or recurrence. About 6% of the patients developed recurrent disease during follow-up. The patients who showed up for a follow-up of 10 years and more were found to be in complete remission.
Conclusion: After thyroid ablation, regular follow-up is necessary for the early discovery and treatment of persistent or recurrent disease. Long-term follow-up can assure a disease-free survival almost similar to that in the general population. Proper education and counseling are necessary for the successful management of these patients.
Radiosynthesis, Quality Control and Biological Evaluation of [ 111 In] 5, 10, 15, 20-Tetra Phenyl Porphyrin Complex in Rats Bearing Breast Tumors as a Possible Imaging/PDT Agent
Agricultural, Medical and Industrial Research School, Karaj, Iran
Aim of the Study: Because of the interesting pharmacological and photodynamic properties of metal-porphyrin complexes and the wide range of their usage in photodynamic therapy treatment, [ 111 In]-labeled 5, 10, 15, 20-tetra phenyl porphyrin ([ 111 In] TPP) was developed as the complex for PDT and SPECT in this work.
Materials and Methods: [ 111 In] indium chloride was prepared by 25 MeV proton bombardment of the enriched cadmium-112 target at a 30 MeV cyclotron. [ 111 In]]-TPP was prepared using freshly prepared [ 111 In] InCl 3 and 5, 10, 15, 20-tetra phenyl porphyrin (TPPH 2) for 2 h at a reflux condition. The partition coefficient was calculated for the compound. The biodistribution of the labeled compound in the vital organs of rats (normal and tumorous) was studied using scarification studies and SPECT up to 24 h and a detailed comparative pharmacokinetic study was performed for [ 111 In] cation and [ 111 In] TPP as well.
Results: The [ 111 In] complex was produced via excellent radiochemical purity (>96% ITLC, >99% HPLC) and the complex was observed to be stable up to 48 h at 37°C.
Conclusion: The results show that a rapid, quantitative preparation of a "carrier-free" [ 111 In] TPP complex is feasible provided that [ 111 In] TPP and its homologs could be suitable lead compounds for developing possible SPECT tracers as well as PDT agents; however, considering the fast wash-out and the short half-life [ 111 In], can be a suitable candidate for labeling of PDT agents as a tracer for accurate biological evaluation of other PDT agents such as Photofrin and its homologs.
[ 64 Cu]-DOTA-PR81 for PET Applications, the Production and Quality Control
B. Alirezapour, A. R. Jalilian, M. J. Rasaee, S. Rajabifar, P. Ashtari, M. Kamalidehghan, S. Moradkhani, A. Sattari, M. R. Aboudzadeh
Nuclear Medicine Department, Agricultural, Medical and Industrial Research School, Karaj, Iran
Aim of the Study: Radiolabeled monoclonal antibodies have shown great promise for cancer diagnosis and therapy. PR81 is a monoclonal antibody that binds with a high affinity to MUC1, which is overexpressed on breast and other tumors. 64 Cu (β+ =17%, β− =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 slower biochemical pathways, such as protein and peptide interactions with cellular targets, and distribution to satellite imaging and therapy centers to be followed. In the present study, we labeled PR81 with 64 Cu via DOTA-NHS (bifunctional chelator) and performed the necessary quality control tests and some in vivo studies in a mouse model to evaluate the complex for radioimmunoscintigraphy of breast cancer.
Materials and Methods: PR81 was conjugated with DOTA-NHS-ester (macrocyclics), purified by molecular filtration. The average number of DOTA conjugated per mAb was calculated and the total concentration was determined by spectrophotometry. DOTA-PR81 was labeled with 64 Cu and then the radiochemical purity, integrity of protein after radiolabeling and immunoreactivity, internalization study and cell cytotoxicity by MCF7 cell line and serum stability of 64 Cu-DOTA-PR81 were determined. The biodistribution studies and radioimmunoscintigraphy were performed in female BALB/c mouse bearing breast carcinoma tumor ( 64 Cu-DOTA-PR81 i.v., 100 μL, 25 ± 5 μg mAb equivalents to 3.2-4.2 MBq, 4 h, 24 h and 48 h).
Results: The radioimmunoconjugate was prepared with a radiochemical purity of 95 ± 1.9% (RTLC). The average chelate to antibody ratio (c/a) for the conjugate used in this study was 6.1 ± 0.44:1. The conjugate was labeled with 64 Cu at a specific activity of 4.8 ± 0.9 μCi/μg. The final compound was stable in the presence of phosphate-buffered saline at 37°C and room temperature. The samples were shown to have similar patterns of migration in the gel electrophoresis. The immunoreactivity of the radiolabeled PR81 ( 64 Cu-DOTA-PR81) toward the MCF7 cell line was determined under conditions of antigen excess in the MUC1 antigen-expressing MCF7 human breast carcinoma cells by using a Lineawer-Burk plot. Under these conditions, the immunoreactivity of the radioimmunoconjugate was found to be 0.76, which is suitable for further imaging studies in animal models and possibly human trials. Internalization assays were performed with the MUC1-expressing MCF7 cell line to determine the internalized activity following in vitro incubation at 37°C as a function of time. Internalized activity for the radiolabeled PR81 reached to the maximum (75-78%) in 4-8 h of incubation at 37°C. After 8 h, the internalized activity was decreased to 47% in 48 h. The biodistribution of the 64 Cu-DOTA-PR81 complex in the mice with breast tumor at 4, 24 and 48 h after intravenous administration is expressed as percentage of injected dose per gram of tissue (%ID/g). Biodistribution and imaging studies at 4, 24 and 48 h post-injection revealed the specific localization of the complex at the site of the tumors. There was no considerable accumulation of hIgG labeled with 64 Cu (as a non-specific antibody) and free 64 Cu at different times at the site of the tumors in comparison with the complex, showing the specificity of the new radiopharmaceutical for breast cancer imaging.
Conclusion: 64 Cu-DOTA-PR81 is a potential compound for molecular imaging of PET for diagnosis and treatment studies and follow-up of MUC1 expression in oncology.
Value of Thyroglobulin Measurement in the Treatment and Follow-Up of Patients with Follicular Differentiated Thyroid Cancer
S. R. Zakavi
Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract: Thyroglobulin, secreted exclusively by thyroid cells, is considered as the most specific tumor marker and is the mainstay in the follow-up of patients with follicular differentiated thyroid cancer (FDTC). In this review, the basic and clinical aspects of thyroglobulin will be discussed. Thyroglobulin is a 660 kD dimer protein, with iodine comprising only 0.1-1% of its weight. The serum level ranges from 3 to 40 ng/mL in normal healthy individuals with no seasonal or diurnal variability. It is degraded by the liver with a serum half-life of 65 h. The Tg level in the serum is dependent on the thyroid cell mass, serum TSH (TSAb and HCG) as well as thyroid cell damage. hTg genes reside in the long arm of chromosome 8q24, and its expression results in a single Tg mRNA of 8.5 kb that can be detected by polymerase chain reaction (PCR) in the peripheral blood.
Immunoreactivity: Thyroglobulin is a large molecule with 40 epitopes. Tg in thyroid cancer has a low iodine content, altered protein structure and low sialic acid. It can be measured with a variety of methods like IRMA, RIA and enzyme-linked immunosorbent assay, but the measurement of Tg must be standardized against the international reference preparation, CRM-457. However, the analytic sensitivity and specificity of the Tg assay vary widely in different laboratories even with the use of new international standards.
Anti-Tg Antibody: Anti-Tg antibody is the most serious problem limiting the clinical value of the Tg assay. Anti-Tg-Ab is rarely detected in a normal child, 10% in normal adults, 15% in females >60 years old and 8-22% in patients with thyroid Ca. After thyroidectomy and radio-iodine ablation, Anti-Tg-Ab disappears in 2-4 years; however, a transient rise during the first few months after RAI therapy is expected. There is no threshold for Anti-Tg-Ab concentration above normal for interference with the Tg assay. The effect of Anti-Tg-Ab is unpredictable with the RIA methods, while it is always unidirectional with the IMA methods, resulting in an underestimation of the Tg level. Hook effect and heterophilic antibodies are other limiting factors with Tg measurement.
Clinical Applications in Patients with DTC: Pre-op setting: Thyroglobulin is secreted more commonly by follicular than by papillary carcinoma, and more frequently in well-differentiated than in poorly differentiated carcinoma. As Tg is increased both in benign and malignant thyroid disease, it is neither sensitive nor specific for the diagnosis of thyroid cancer and its measurement is not recommended before surgery. However, Tg measurement in FNA aspirates is recommended in the evaluation of cystic lymph nodes before surgery.
Before Radio-Iodine Ablation: Measurement of Tg before I-131 therapy in a hypothyroid state (first Tg) has a very valuable prognostic significance. In a study, the first Tg levels of >70 ng/mL measured 40 days after surgery had a PPV of more than 90% for the prediction of metastasis. Multiple other studies confirmed the finding with different thresholds, and it has a potential promising value in the selection of patients for high- or low-dose radio-iodine therapy.
Post-Ablation Follow-up: It is believed that the Tg level should be undetectable after successful ablation. Tg levels of >1 ng/mL have been considered as a marker of remnant disease and levels of >10 ng/mL may be considered as an indication for further treatments. However, a low on-T4-Tg level does not exclude metastasis. An on-T4-Tg <0.1 ng/mL was associated with detectable off-T4-Tg in 3.5% of the patients and detectable disease in less than 1% of the patients. However, lymph node metastasis is frequently reported with low levels of Tg. Therefore, undetectable off-T4-Tg associated with negative neck ultrasonography is considered as an indication of complete response in 99% of the cases. In a meta-analysis, the sensitivity and specificity of the Tg assay to detect persistent disease was reported to be 95% and 96%, respectively. Many authors reported that a rising Tg is more specific than a single Tg measurement. A progressive increase in the Tg level strongly suggests progressive disease. This approach brought a new idea of Tg doubling time (Tg-DT) that is used for diagnostic and prognostic purposes. Tg-DT <1 year was associated with decreased disease-specific survival (50% at 10 years) as well as more positive FDG-PET images. Patients with Tg-DT between 1 and 3 years had 95% and those with Tg-DT >3 years had 100% disease-specific survival at 10 years.
Ultrasensitive Tg: Measurement of Tg with ultrasensitive methods (in subnanogram levels) is recently the focus of many researches and could decrease the need for TSH stimulation in low-risk patients. An on-T4-Tg level of <0.1 ng/mL was associated with recurrence in less than 1% of the patients, and the Tg-DT approach is applied to the ultrasensitive Tg as well.
Serum Tg mRNA Assay: Tg mRNA can be measured in peripheral blood using the reverse transcriptase-PCR method. It is reported to be more sensitive than the Tg assay and is not affected by anti-Tg-Ab and not dependent on the TSH level. However, the reported specificity (~24%) is too low to consider it in the routine follow-up schema.
Tg and Whole Body Iodine Scan (WBIS): Undetectable Tg levels may be seen in patients with lymph node metastasis; however, iodine avid distant metastasis is nearly always associated with elevated Tg. If off-T4-Tg was undetectable in a patient with positive WBIS, false-positive findings should be excluded before any attempt for I-131 treatment of the patient. On the other hand, about 15% of the patients with elevated on-T4-Tg may have negative WBIS. A false-negative scan may be the result of iodine excess, inadequate TSH stimulation, suboptimal technique and dedifferentiation of tumor. Measurement of urinary iodine as well as ultrasonography or non-contrast CT is the first step in the approach to these patients followed by a surgical approach in patients with detectable mass and PET/computed tomography in patients with non-detectable mass and Tg levels of more than 10 ng/mL. Thyroglobulin is the most important marker in the treatment and follow-up of patients with DTC and could be used for diagnostic and prognostic purposes. It should be measured using a single method with a kit standardized against CRM-457 and preferably in a single laboratory. New ultrasensitive Tg assays may significantly decrease the need for TSH stimulation in low-risk patients.
Treatment Planning in Radionuclide Therapy
Medical Physics, Tarbiat Modares University, Tehran, Iran
Abstract: Nuclear medicine was initiated with a mixture of therapeutic and diagnostic procedures. The introduction of 99m Tc, invention of gamma camera and development of tomographic techniques significantly promoted the diagnostic aspects of nuclear medicine. Later, positron emission tomography (PET) and production of FDG further promoted the diagnostic features of nuclear medicine. However, recent advances in immunotherapy using monoclonal antibodies opened the door to a new era for the therapeutic application of nuclear medicine. Radioimmunotherapy is a technique to specifically attack the target cell with the radiation emitted from charged particles from radioisotopes. It is probably the ideal objective of targeted therapy and potentially the most effective technique for the treatment of spreading cancer and metastatic tumors. However, success of the technique is yet limited due to certain problems. Radionuclide therapy, in essence, is a brachytherapy in which the objective is delivering an accurate amount of radiation dose to the target while minimizing the dose to the non-target tissues. However, in comparison with external beam radiation therapy, this goal is very hard to achieve in internal radiation therapy. In external beam radiation therapy, almost all the physical aspects of radiation (e.g. exposure, duration, dose) are under the control of radiotherapists. However, almost nothing would be under the control of the physician after administration of the radiopharmaceuticals to the patient's body. In external radiation therapy, dosimetry is based on the measurements using physical instruments while in radionuclide therapy, dose to the tissues cannot be measured and can only be estimated using mathematical techniques. At present, the most accurate method of internal dose estimation for individual patients is the Mote Carlo technique. However, it requires quantitative images of SPECT or PET, which are not yet available with adequate accuracy. Moreover, it is not clear whether the radiobiological bases of internal and external radiation therapy are similar. In external beam radiation, the absorbed dose rate is very high (1-5 Gy/min) and an almost uniform dose of radiation can be delivered to the tumors. However, in internal radiation therapy, the exposure rate is much lower (2-8 Gy/day) and dose distribution is significantly non-uniform. Even at equal radiation doses, the effects of DNA repair, cell cycle synchronization, radiation resistance and re-oxygenation are different at low and high radiation dose rate and, therefore, no similar response is expected even in identical cell lines. From the physical point of view, there are also some differences between internal and external radiation therapy. The main effect of radiation damage is due to the indirect effect of radiation via production of δ-radiation. It is believed that electrons with a kinetic energy of 10 eV are destructive to the DNA. Therefore, irrespective of the dose rate, the energy distribution of delta electrons can be different not only in internal and external radiation but also for the different radionuclides. Therefore, treatment planning for radionuclide therapy is quite complicated compared with conventional radiotherapy. We have to consider the fact that external beam radiation therapy has a long history of research and application but radionuclide treatment planning is only in its primary stages.
3-Benzyl-3-Hydroxy- 1,5-Dimethyl-1,3-Dihydro-Indol-2-One Labeled Gallium-67 and 68 as Potential Anticancer Agents
M. Ghandi, S. Feizi, F. Ziaie
Agricultural, Medical and Industrial Research School, Karaj, Iran
Aim of the Study: Oxindole natural products continue to gain special attention due to their chemical and biological potencies such as anti-HIV, anti-oxidant and outstanding anti-cancer properties. This work covers the synthesis, characterization and isolation of a novel compound, "3-Benzyl-3-hydroxy-1,5-dimethyl-1,3-dihydro-indol-2- one," followed by the biological evaluation of its labeled Gallium-67 and 68 complex.
Materials and Methods: [ 67 , 68 Ga] labeled 3-Benzyl-3-hydroxy-1,5-dimethyl-1,3-dihydro-indol- 2- one was prepared using freshly prepared [ 67 , 68 Ga] GaCl 3 and 3-Benzyl-3-hydroxy-1,5-dimethyl-1,3-dihydro-indol-2- one for 60 min under reflux conditions (radiochemical purity: >99% ITLC, specific activity: 12-14 GBq/mmol). The stability of the complex was checked in the final formulation and human serum for 48 h. Biodistribution studies of the labeled compound in the vital organs of rats bearing fibrosarcoma tumors were performed using scarification, coincidence imaging and SPECT up to 24 h. A detailed comparative pharmacokinetic study is performed for 67 Ga cation and labeled compound up to 24 h.
Results and Conclusion: The complex is mostly washed out from the circulation through the kidneys and liver. The images of the radiolabeled compound demonstrated a high uptake in the tumor region 2-24 h post-injection, which is in agreement with the biodistribution data. The results demonstrate that the oxindole system goes to an enhanced target to a non-target ratio of injected dosage of this compound.
Withholding Radioactive Iodine Therapy in Thyroid Cancer Patients: A Drawback
H. Caldito, E. Barrenechea
Nuclear Medicine, Veterans Memorial Medical Center, Quezon City, the Philippines
This study was conceptualized with the present guidelines limiting the use of radioactive iodine for ablation of thyroid cancer remnants. Truly, the old adage treatment triad of total surgery, radioactive iodine and lifetime thyroid hormone suppression should be applied to almost all cases with few exceptions and, better still, on a case-to-case basis. It is good to know the guidelines set by the specialty societies to guide us on what to do. However, we must be realistic considering the locality we practice and the cases that we see. In a 10-year follow-up, we have 18 patients who were not given RAI treatment after surgery for an average of 3-10 years and only after such time were these cases referred to us by their surgeons and found to have metastases or recurrence of the disease. Fourteen of these patients were only maintained on thyroid hormone, which was not even for suppression, and four patients did not have any maintenance. Six patients had bone metastases, three on the hips, three with multiple skeletal sites as in vertebra and pelvis and three had widespread metastases in the soft tissues and bones. The rest of the patients had cervical and lymph nodes metastases in the neck. This 10-year study to determine which patient must get therapy strengthened the premise that the following factors should be taken into consideration: Age, extent of the disease, histopathology and adequacy of the surgery/neck dissection. In our cases, the histopathology was predominantly papillary with follicular variant (nine patients) or eosinophilic (one patient), Hurthle (two patients), sclerosing type (three patients) and tall cell findings (three patients). The age group was the late 50s to 70 years of age; 12 patients were female and five were male. Except two patients who had lobectomy, most of them underwent near-total thyroidectomy, five of whom had at least two completion surgeries.
Conclusion: This study supports that the comprehensive management of thyroid cancer with the above features should be total thyroidectomy, radioactive iodine ablation and lifetime thyroid hormone suppression.
Evaluation of the Pharmacokinetics of 188 Re-KHEDP and 99m Tc-HDP in Humans
M. Smolyarchuk, T. Kochetova, V. Krylov, A. Alexandrova, G. Davydov, E. Davydova
Nuclear Medicine Department, Medical Radiological Research Center, Obninsk, Russia
Aim of the Study: Individual dose planning is one of the most topical problems in today's radionuclide therapy. 188 Re-labeled radiopharmaceuticals can provide high doses to regions of interest, thanks to high beta-particle energy; therefore, dose planning becomes very important to avoid side-effects. 188 Re-potassium hydroxyethylidene diphosphonate (HEDP) has a theragnostic pair when labeled with Technecium-99m ( 99m Tc-HDP). The aim of this work is to evaluate the pharmacokinetics of 188 Re-HEDP in humans and to evaluate the predictive value of a 99m Tc-HDP preliminary scan for radionuclide therapy planning.
Materials and Methods: Eight patients having painful bone metastases from breast cancer, prostate cancer, thyroid cancer and gastric cancer were studied. Before radionuclide therapy, patients had scintigraphic studies: Static images of the pelvis, including the kidneys, were made at 1, 3 and 24 h and whole body scan was performed at 3 h after the injection of 800-1000 MBq of 99m Tc-HDP. Three to 6 days later, 2-3 GBq of 188 Re-HEDP was injected intravenously. Static images at 1, 3, 24 and 48 h and whole body scan at 22-24 h after administration were performed. The acquired images were assessed visually and semiquantitatively using a differential uptake coefficient (DUC), which was calculated as a percentage of the lesion/normal bone uptake. Effective half-time (T 1/2 ) of the isotopes from time of maximum uptake was computed for both datasets using exponential estimation in metastatic lesions, healthy bone and soft tissue background.
Results: Whole body scans with both radiopharmaceuticals showed the same number and localization of bone pathologic uptake lesions in all patients. DUCs were the same in five patients (140-390%), higher with 188 Re-HEDP in two patients (higher up to 80%) and higher with 99m Tc-HDP in one patient (higher up to 30% difference). T 1/2 of 188 Re-HEDP in metastases is 36.7 ± 3.4 h and in the bones is 31.5 ± 2.8 h. T 1/2 of 99m Tc-HDP in metastases is 6.3 h, in bones is 4.8 h and in soft tissue is 7.3 h. In addition, whole body scans with 188 Re-HEDP showed a high uptake in the kidneys in all patients (220-420% over the background), moderate uptake in the liver in seven patients (160% ±10%) and intensive uptake in the thyroid in two patients (210-380% over the background).
Conclusion: 188 Re-HEDP shows intensive uptake in bone metastases similar to 99m Tc-HDP, and it washes off from the lesions significantly slower than from the healthy bones. Good correlation between uptake of these radiopharmaceuticals indicates that bone scan with 99m Tc-HDP can be used to predict the 188 Re-HEDP uptake in the bones and plan individual doses for radionuclide therapy more effectively. However, 188 Re-HEDP has a lower T 1/2 and its uptake in the liver and thyroid indicated high binding to blood proteins and decomposition of a radiopharmaceutical in vivo, which needs further investigation.
Evaluation of 188 Re-KHEDP (Phosphoren) for Palliative Treatment in Patients with Bone Metastases
V. Krylov, T. Kochetova, M. Smolyarchuk, V. Petriev, V. Kanygin, A. Alexandrova, A. Shurinov, A. Ivanovich
Radionuclide Therapy Department, Medical Radiological Research Center, Obninsk, Russia
Aim of the Study: Bone metastases are common in various cancer diseases. Often, they cause severe pain syndromes and lead to a significant decrease in the life quality of patients. Radionuclide therapy (RNT) with bone-seeking radiopharmaceuticals (BS RPC) has shown its effectiveness in the palliative treatment of such patients. However, the development of new radiopharmaceuticals and methods of RNT may improve the efficacy of treatment of patients with bone metastases. We work on the clinical investigations of new Russian therapeutic BS RPC Phosphoren ( 188 Re-KHEDP). The main aim of this work is to study the possibilities of the clinical application of a new Russian radiopharmaceutical, Phosphoren, for the palliative treatment of patients with bone metastases, to evaluate its pharmacokinetic characteristics, toxicity and pain syndrome suppression in patients.
Materials and Methods: Twelve patients with bone metastases and pain syndrome were treated using Phosphoren. All of them were subjected to clinical and laboratory tests, including bone scan with diagnostic radiopharmaceutical Phosphotech ( 99m Tc-HEDP), which is a theragnostic pair for Phosphoren. Phosphoren was obtained from the radionuclide therapy department of MRRC from the 188 Re eluate produced on a stationary generator in the Federal Centre for Design and Development of Nuclear Medicine FMBA of Russia (Moscow) and lyophilisate of the same production by heating in a water bath for 30 min. Two to 3 GBq of Phosphoren was administered intravenously in 15-20 mL of saline solution. Biodistribution of the radiopharmaceutical was assessed by scintigraphy methods at 1, 3, 24 and 48 h after injection. Toxicity was assessed by the general condition, physical data and laboratory analysis of the blood of the patients. Evaluation of the effectiveness was assessed by changes of pain syndrome and the abolition of analgesic drugs. Follow-up evaluation was performed seven and more times for more than 3 months.
Results: All patients showed a high uptake of the therapeutic radiopharmaceutical Phosphoren in the metastatic lesions on scintigraphy. In 1 h, p/a accumulation of the drug in bone metastases, in the area of injection, in blood and in the organs of the urinary system was observed. In the following scans, preferential accumulation in the metastatic foci and elimination through the urinary system were noted. Also, after 3 h, low accumulation in the liver was presented on the scans. According to a comparative analysis of Phosphoren and Phosfotech, their biodistribution characteristic correlates well. According to the results of a safety assessment of 12 patients, a relative myelotoxic transient response was noted, manifested in the form of mild thrombocytopenia and erythrocytopenia. The level of platelets and RBC returned to the initial state in 5 weeks in a majority of the patients. Seven of 12 patients had significant pain reduction, reducing the need for analgesic drugs. Four patients had stabilization or minimal pain reduction. One patient had further development of pain. An analgesic effect developed almost immediately after administration.
Conclusion: Phosphoren is a promising radiopharmaceutical and can be used for the palliative treatment of patients with bone metastases and pain syndrome, although it needs further investigation.
Determining the Differences in Whole Body Radio-Iodine Clearance using Dose Rate Monitoring in Patients Undergoing High-Dose Radioactive Iodine Therapy: A Single Institution Experience
A. Sunga, M. Torres, R. M. Goco, E. Barrenechea
Department of Nuclear Medicine, St. Luke's Medical Center, Quezon City, Philippines
Aim of the Study: In the Philippines, patients undergoing radio-iodine therapy using at least 15 mCi of 131 I are admitted and are discharged only when their dose rate measurement at 1 month is ≤ 25 μSv/h. In theory, the total amount of administered radio-iodine in the body determines the dose rate measured at a given distance from the patient. This is, however, dependent on how much thyroid tissue is present and how well the radio-iodine is cleared from the body. In post-thyroidectomized thyroid cancer patients, because the volume of the remaining thyroid tissue is minimal, the ultimate determinant of the dose rate measurements would be radio-iodine clearance. This is important as poor radio-iodine clearance is associated with the development of side-effects such as nausea, neck swelling/tenderness, dryness of the mouth, swelling/tenderness of the salivary glands, taste disturbances and dry eyes. This study was conducted to determine whether there is a significant difference in the body clearance among post-thyroidectomized patients given 100 or 200 mCi 131 I based on their dose rate monitoring at 1 month.
Materials and Methods: Thirty consecutive thyroid cancer patients who were admitted for RAI therapy using either 100 mCi (n = 25) or 200 mCi (n = 5) were included in this study. After oral RAI administration, dose rate measurements at 1 month were acquired at the level of the umbilicus. Daily dose rate monitoring was subsequently performed taking note of the number of days it took for the 1-month dose rate to reach ≤25 μSv/h, and this was noted for each patient.
Results and Conclusion: Among patients given 100 mCi 131 I, the immediate dose rate at 1 month ranged from 80 to 190 μSv/h, while among those given 200 mCi, it was 180-340 μSv/h. However, there was no significant difference in the number of days elapsed to achieve a 1-month dose rate of 25 μSv/h between patients who received 100 mCi and those who received 200 mCi 131 I. In both groups, the average was 2-3 days. This may be due to the current practice among physicians performing RAI therapy of advising patients to increase their oral fluid intake and take sour candies/fruits as prophylaxis against the possible side-effects of RAI therapy. Other factors that may also affect the dose rate monitoring, such as frequency of bowel movement, micturition and whole body baths, were not factored in this study.
Activity in Urine Following 177 Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy
I. Vito, J. Jones, S. Parker, S. Navalkissoor
Nuclear Medicine Department, Royal Free Hospital London NHS Foundation Trust, London, United Kingdom
Aim of the Study: To determine the urinary excretion fraction and rate of urinary excretion in metastatic neuroendocrine tumor patients administered 7.4 GBq of 177 Lu-DOTA-Octreotate therapies through an assay of their urine samples.
Materials and Methods: In all patients, the normal baseline renal function was recorded. Patients had Lu-177 DOTATATE administered along with renal protection, which included fluids containing amino acids with at least 25 g of Lysine and Arginine, which was commenced at least 1 h before the administered radiopharmaceutical. Urine samples post-therapy were collected in 16 patients. Patients were asked to collect urine samples in separate bottles during the duration of their overnight stay (urine bottles were separated into 3-h intervals). Urine samples were then placed in a refrigerated store for at least one half-life (6.7 days) to allow activity reduction before handling and analysis. The gross weight of each urine container was measured and the volume of urine was calculated. The urine container was agitated to ensure homogeneity and 10 mL (mean sample volume 10.46 mL) was pipetted into a sample container. Each sample was assayed using an isotope calibrator using a Lutetium-177 calibration factor traceable to the National Standards. Activity measured was decay corrected to give the activity excreted at a time midway through the collection time period. Analysis of the activity excreted over time showed that this can be approximated by a biexponential decay curve. The amount and fraction of the administered activity of the excreted urine was calculated. We determined the amount and fraction of activity excreted in the first 3 h and the first 6 h.
Results: The mean administered activity was 7591 MBq (range 6773-8293 MBq). The mean urine excreted was 4092 MBq (range 517-5607 MBq). The mean percentage of urine excreted in the first 24 h was 56.6% (range 7.6-72.8%). Fifteen of 16 patients had a urinary excretion fraction of 37% or more. Within the first 3 h, the mean percentage urine excretion was 54.8% (range 37.7-67.4%). Within the first 6 h, the mean percentage urine excretion was 81.8% (range 68.1-90.7%). Between 6 and 24 h, the mean activity excreted was 718 MBq (range 165-1156 MBq).
Conclusion: The mean percentage urinary excretion was 56%, with the majority of individual patients having excretion values of between 40% and 60%. Most of the urinary excretion occurs within the first 6 h after therapy; thus, if outpatient PRRT is being considered, this should be considered as the minimum time that the patient should remain within the unit.
Clinical Results of A Combined Therapy of Painful Multiple Skeletal Metastases by Samarium-153 Oxabifore Administration and Pamindronate Injection
D. Arybzhanov, N. Rasulova, O. Nurgali
Chemotherapy and Endovascular Oncology, South Kazakhstan Oncological Clinic, Shymkent, Kazakhstan
Aim of the Study: To assess the clinical results of combined therapy by Sm-153 oxabifore and Pamindronate (bisphosphonate) administration.
Materials and Methods: Twenty-three patients, all female, aged between 26 and 82 years (mean age 55.3 + 11.2 years) with multiple skeletal metastases from breast carcinoma (20 patients), lung carcinoma (one patients) and kidney cancer (two patients) were enrolled in the study. Carcinoma was confirmed by whole body bone and computed tomography scans. All patients received combined therapy by the administration of Sm-153 oxabifore at a standard bone palliative dose of 37 MBq/kg body weight. Two weeks after radionuclide therapy, the patients received an injection of 90 mg Pamindronate (bisphosphonate) every 28 days. Their mean objective pain score according to the 10-score system before therapy was 6.6 + 1.5 (range 5-9). The Karnofsky performance status was 61.5 + 10.3 (range 40-80). The objective pain score and performance status were estimated at 4 weeks after radionuclide therapy and at 2 weeks after Pamindronate administration, respectively.
Results: Four weeks after radionuclide therapy and 2 weeks after Pamindronate administration, there was a statistically significant reduction of the objective pain score to 0.5 + 0.2 (range 0-2) and the Karnofsky performance status increased to 96 + 5.8% (range 80-100%), P <0.0001.
Conclusion: Combined therapy using Samarium-153 oxabifore with the administration of Pamindronate had shown promising, effective results in decreasing the objective pain score and increasing the quality of life. However, studies in larger populations are needed.
Introducing I-131 MIBG Therapy in Pakistan: Steps Taken to Administer the First Therapy in a Patient Having Metastatic Pheochromocytoma
S. Butt, S. Fatima, G. Jameel, N. Marwat, J. Irfan
Nuclear Medicine Department, Nuclear Medicine, Oncology and Radiotherapy Institute, Islamabad, Pakistan
Neuroblastoma, pheochromocytoma and paraganglioma are considered fatal diseases for a large percentage of patients, especially those having high-risk features of disease who become resistant to conventional therapy. The standard treatment options for metastatic pheochromocytoma include surgery and palliative therapy. Multiple chemotherapy agents have been tried with limited success. 131 I-MIBG radiation therapy has been used for the treatment of MIBG-avid metastases. Approximately 60% of the metastatic pheochromocytoma sites are MIBG-avid. Today, radiopharmaceutical therapy is the fastest growing branch of nuclear medicine. However, its practice in developing countries is only beginning to gain ground after years of trailing behind its use in the developed world. 131 I-MIBG has been widely used throughout the globe for the treatment of patients with malignant pheochromocytoma. However, it had not been tried yet in Pakistan, although there are many centers in the country that are registered for radionuclide therapy and are performing therapies for carcinoma thyroid. Because of the unavailability of a multidisciplinary team to cope with the adverse effects of catecholamine-secreting tumors and lack of equipment for vigilant patient monitoring with all radiation protection precautionary measures, this therapy was never tried. Patients had to go abroad to get treatment, which is expensive, and this opportunity is available to a selected class; others were treated with chemotherapy, considering it to be the only available option. For the first time in Pakistan, a case of chemo-resistant metastatic pheochromocytoma was successfully treated with 7.4 GBq 131 I MIBG therapeutic dose at our institute. This patient again received a second dose in our department. Our hospital is receiving referrals for the therapy due to the publicity of the event. Keeping this as an example, other radionuclide therapies might be planned to be started in developing countries. The motivation of the nuclear physicians of the region is of utmost importance. This will require efforts regarding the availability of radionuclides, availability of radiation protection equipment, availability of isolation rooms and training of nuclear physicians, medical physicists and other related hospital staff.
AHCC: Impact on the Immunological System of Patients with Disseminated Neuroendocrine Tumors After Treatment with the Radioisotope preparation ( 90 Y-DOTA-TATE) - An Initial Report
N. Szalus, R. Zdanowski, S. Lewicki, D. Szydlarska, T. Budlewski
Radionuclide Therapy and Nuclear Medicine, Central Clinical Hospital of Ministry of Interior, Warsaw, Poland
Aim of the Study: Active hexose correlated compound (AHCC) is an alfa-glucan-rich nutritional supplement produced from the mycelia of shiitake (Lentinula edodes) of the Basidiomycete family of mushrooms. Human clinical studies have shown that AHCC significantly improves immune response, increases and maintains normal NK cell activity and enhances macrophage and T-cell activity. The aim of this study is to assess the efficacy of AHCC in neuroendocrine tumor (NET) patients on the immunological system 3 months after the last dose of 90 Y-DOTA-TATE. The main purpose of our study in the future will be the evaluation of the influence of AHCC on the immunological profile, time to progression, progression-free survival, overall survival and response rate.
Materials and Methods: We evaluated three patients with histopathologically confirmed NETs, who were included in the study. These patients were treated with four doses of 90 Y-DOTA-TATE (3.7 GBq/m 2 /dose) in 8-10-week intervals. Control computed tomography (CT) and PET/CT with somatostatin analog 68 Ga-DOTA-TATE were conducted 3 months after the last dose of 90 Y-DOTA-TATE. Patients took AHCC doses in the amount of 6 g daily (3 × 2 g), 40 min before meals. A local ethics committee approval was obtained before commencing the study.
Results: All results are presented as medium results. Three months after the last dose of 90 Y-DOTA-TATE, the following was found: the CD3+, CD3+ CD4+, CD3+ CD16/56+ and CD4+ CD25++FoxP3 + cells decreased by 4.91%, 36.27%, 14.48% and 28.2%, respectively; and the CD3+ CD8+ and CD3-CD16/56+ cells increased by 60.43% and 18.84%, respectively. In PET/CT and CT, partial responses were revealed after this combined therapy ( 90 Y-DOTA-TATE + AHCC).
Conclusion: AHCC is a promising extract that increases the amount of CD3+ CD8 + and CD3-CD16/56+ cells and decreases CD4+ CD25++FoxP3+ in patients with NETs. In further studies, we want to determine whether a decrease in CD3+, CD3+ CD4+ and CD3+ CD16/56+ cells is important for NET patients and to check whether these results will be confirmed in others patients.
Follicular Thyroid Cancer Presenting with Skull Metastases Without the Uptake of Radioiodine
Medical Physics/Radiology sub Nuclear Medicine, Faculty of Medicine Andalas University/Dr. M. Djamil Hospital, Padang, Indonesia
Abstract: Distance metastases of differentiated thyroid cancer (DTC), such as of the follicular type to the skull, is relatively rare. Nagamine et al. reported only 2.5% of such cases. Also, skull metastases occurred a long time after the initial diagnosis. Patients with DTC who undergo total or near-total surgery are then treated with radioiodine ( 131 I), which is essential to treat metastatic disease. About 5% of the patients who develop bone metastases show an inability to accumulate radioiodine.
Case Report : A 51-year-old woman was initially diagnosed as an adenomatous goiter. Eight years after the first diagnosis, she complained of a lump in her skull that was found to be due to follicular thyroid cancer and underwent a total thyroid surgery, followed by 3.7 GBq 131 I treatment. Four years after the operation, she came back with a relapse of the lump. Blood tests after 4 weeks of thyroxine withdrawal showed TSH: 2.771 mU/L, Thyroglobulin: 1.78 ng/mL and negative anti-thyroglobulin. Thyroid scintigraphy showed no uptake in the thyroid bed. 131 I whole body scan did not show skull uptake and bone scintigraphy demonstrated high uptake in the skull.
Discussion: Follicular thyroid cancer is a subtype that is slow growing and is associated with good prognosis; skull metastases occur a long time after the diagnosis. It is difficult to make the distinction between benign and malignant follicular thyroid tumor. Furthermore, the prognosis is poor in the presence of distance metastases. Cell dedifferentiation leads to a loss of the cell's ability to accumulate radioiodine. About 5% of patients will develop metastases and show an inability to accumulate radioiodine. Identifying the genes expressed in follicular adenomas and carcinomas of the thyroid will permit molecular differentiation in suspicious cases. Furthermore, the unresponsiveness of radioiodine can be caused by cell dedifferentiation. This is related to poor prognosis in patients with bone metastases. Understanding the molecular aberration in thyroid has led to a promising future in targeting therapies of unresponsive radioiodine.
High- vs. Low-Dose Radio-Iodine Therapy for Initial Remnant Ablation of Post- Thyroidectomised Patients with Differentiated Thyroid Cancer: A Meta-Analysis
J. Mendoza, I. Bandong
Department of Nuclear Medicine, St. Luke's Medical Center, Quezon City, the Philippines
Abstract : The use of high- or low-dose radio-iodine therapy (RAIT) for initial remnant ablation in post-thyroidectomised patients diagnosed with differentiated thyroid cancer (DTC) with no distant metastases has long been a subject of much debate. Conflicting conclusions/recommendations have been presented by a wide array of both randomized controlled trials (RCTs) and observational studies. Meta-analyses and systematic reviews have been made to consolidate the available researches and to arrive at a pooled analysis and conclusion. However, the available meta-analyses and systematic reviews tend to combine RCTs and observational studies, or use RCTs alone without due regard to differences in study design. Hence, a more focused meta-analysis of the available RCTs alone is in order. This meta-analysis aims to determine the presence of a compelling difference between the initial remnant ablation success rates of high- and low-dose radio-iodine therapy in post-thyroidectomised DTC patients without distant metastasis using only available randomized clinical trials.
Search Methods: An extensive search of the PubMed and Cochrane Central register of RCTs (up to August 2013) was performed by two reviewers (JM and IB). The following key words were used to screen the PubMed and Cochrane databases: ("randomised controlled trial" OR "RCT") AND ("Radio-iodine ablation" OR "Radio-iodine therapy") AND ("well differentiated thyroid cancer" OR "papillary thyroid cancer" OR "follicular thyroid cancer"). This was completed by a hand search of the references from relevant articles and review papers published from 1996 to 2012.
Selection Criteria: The two reviewers (JM and IB) independently selected the eligible studies, with disagreement resolved by consensus. The inclusion criteria were as follows: (a) RCT,(b) post-thyroidectomised adult subjects diagnosed with well-differentiated thyroid cancer with no evidence of distant metastases and (c) subject randomization into 30-50 mCi or 100 mCi 131 I treatment groups. Studies were excluded if (a) the full text of the study was not available, (b) the study was in a language other than English and (c) if the data on relative risk were not available or could not be derived from the study. Of the eight published RCTs on radio-iodine therapy as of August 2013, only five were eligible for this meta-analysis; namely, those by Johansen et al. (1991), Bal et al. (1996), Zaman et al. (2006), Mäenpää et al. (2008) and Caglar (2012).
Data Collection and Analysis: The same two reviewers independently extracted data from the full text of the selected five studies. Two-by-two tables comparing the frequencies of successful and failed remnant ablation using low-dose (30-60 mCi) and high-dose (~100 mCi) RAIT were derived from the published results of the included studies. Using Review Manager (RevMan) software version 5.2.6, weighted and pooled relative risks for successful remnant ablation were computed via the Mantel-Haenszel method using a fixed effects model (α =5%). Subgroup analyses were performed based on different definitions of a successful remnant ablation.
Main Results: Three of the included studies tended to favor the use of high-dose RAIT, while the remaining two favored otherwise. However, the pooled relative risk (-0.03) was statistically insignificant (P = 0.54) and had a poor precision (95% confidence interval of -0.12, 0.06). This was also noted when a successful remnant ablation was defined as having a negative whole body scan (WBS) and undetectable serum Tg <10 ng/mL (P = 0.27) or <2 ng/mL (P = 0.25) after TSH stimulation 3-8 months post-RAIT (pooled relative risks of -0.06 and -0.08, and 95% confidence intervals of -0.15, 0.04 and -0.22, 0.06, respectively). However, using only a negative TSH-stimulated follow-up WBS, the pooled response rate improved to -0.11 (95% confidence interval of -0.24, 0.01) while still remaining insignificant at the 5% confidence level (P = 0.07). Using RCTs that compared high- and low-dose RAIT for remnant ablation of DTC, there was an apparent trend favoring higher success rates using high-dose RAIT. However, more well-designed RCTs are needed to adequately evaluate this issue.
Heterogeneity Analysis of [ 18 F]-FDG Uptake in Differentiating between Metastatic and Inflammatory Lymph Nodes in Adenocarcinoma of the Lung: Comparison with Other Parameters and its Clinical Application
H. Budiawan, G. J. Cheon, H. J. Im, S. J. Lee, J. C. Paeng, K. W. Kang, J. K. Chung, D. S. Lee
Department of Nuclear Medicine, Seoul National University, Seoul, Korea
Aim of the Study: Lymph node (LN) characterization is very crucial, which determines the stage and treatment decisions in patients with lung cancer. Although [ 18 F] FDG PET/CT has a higher diagnostic accuracy in LN characterization than anatomical imaging, differentiating between metastatic and inflammatory LNs is still challenging because both could show high [ 18 F] FDG uptake. The purpose of this study was to assess whether the heterogeneity of the [ 18 F] FDG uptake could help in differentiating between metastatic and inflammatory LNs in lung cancer, compare this with the other parameters and propose a diagnostic approach.
Materials and Methods: A total of 44 patients with adenocarcinoma of the lung, who underwent pre-operative [ 18 F] FDG PET/CT without having any previous treatments and were revealed to have [ 18 F] FDG-avid LNs, were enrolled in the study. There were 52 pathology-proven metastatic lymph nodes in 26 subjects. The pathology-proven metastatic LNs were compared with 42 pathology-proven inflammatory/benign LNs in 18 subjects. Coefficient of variation (CV) was used to assess the heterogeneity of [ 18 F] FDG uptake by dividing the standard deviation of the standardized uptake value (SUV) by the mean SUV. The volume of interest was manually drawn based on the combined CT images of [ 18 F] FDG PET/CT (no threshold was used). Comparisons were made with maximum standardized uptake values (SUVmax), visual assessment of [ 18 F] FDG uptake, longest diameter and maximum Hounsfield unit (HUmax).
Results: Metastatic lymph nodes tended to have a higher CV compared with the inflammatory LNs. The mean CV of the metastatic LNs (0.30 + 0.08; range: 0.08-0.55) was higher than that of the inflammatory LNs (0.17 + 0.06; range: 0.07-0.32; P <0.05). On receiver-operating curve analysis, the area under curve was 0.901, and using 0.20 as the cut-off value, the sensitivity, specificity, PPV, NPV and accuracy were 88.5%, 76.2%, 82.2%, 84.3% and 83.0%, respectively. The accuracy of CV was slightly higher than that of SUVmax and diameter, but significantly higher than that of visual assessment and HUmax. A diagnostic strategic approach (by considering the value of CV, SUVmax and diameter) revealed a higher sensitivity, specificity, PPV, NPV and accuracy (92.3%, 83.3%, 87.3%, 89.7% and 88.3%, respectively).
Conclusion: In patients with adenocarcinoma of the lung having no prior treatments, metastatic LNs showed more heterogeneous [ 18 F] FDG uptake than inflammatory LNs. Measuring the CV of the SUV derived from manual VOI can be helpful in determining the metastatic lymph node of adenocarcinoma of the lung. Including diagnostic criteria of CV into the diagnostic approach can increase the accuracy of lymph node status.
Radiation Dose Estimates of Technologists in the Positron Emission Tomography (PET) Center at the St. Luke's Medical Center
J. M. Dela Cruz
PET Center, St. Luke's Medical Center, Quezon City, Philippines
Radiation dose estimates to technologists in the St. Luke's Medical Center Positron Emission Tomography (PET) Center were obtained covering all the activities performed with the administration of 18 F-Fluorodeoxyglucose (FDG). Different areas inside the center were characterized and identified to estimate the possible radiation exposure of the patients' comforters and medical practitioners, among others. Data from 75 [ 18 F] FDG-injected patients were obtained. The results showed that the technologists received an estimated dose equivalent to 8.66 μSv per patient and, for the 477 patients performed on an average for a year, this translates to 4.13 mSv/year. These are well within the suggested dose limits for occupationally exposed individuals and comparable to the doses received by technologists in a conventional nuclear medicine unit.
Role of Myocardial Perfusion Imaging in Acute Coronary Syndrome
Nuclear Cardiology, PINUM Cancer Hospital, Faisalabad Jail Road, Pakistan
Aim of the Study: In the emergency department, most of the patients present with acute chest pain. In case of non-diagnostic electrocardiogram (ECG) and cardiac enzymes, a cardiologist faces a dilemma in accurately categorizing the patient in high or low probability. The aim of our study was to evaluate the role of myocardial perfusion imaging (MPI) in patients with acute coronary syndrome (ACS) to categorize them in low- and high-risk groups.
Materials and Methods : A total of 44 patients were divided into three groups on the basis of their probability of having ACS according to the clinical information, i.e. nature of chest pain, ECG findings, cardiac enzyme levels, age and sex. An arbitrary score was assigned to each patient. Patients in the low and intermediate probability groups were injected with Tc99m-MIBI within 6 h of onset of chest pain and imaging was performed 3-5 h after the injection. Imaging in the high-probability group was performed at the time of discharge. Four weeks after the acute event, all the patients underwent stress MPI.
Results: All the patients with a low probability of ACS (n = 15) showed negative resting scans. On stress MPI, three patients showed new defects. All patients with a high probability of ACS (n = 15) were positive on the resting MPI. On stress MPI, five patients showed no change from resting MPI while 10 patients showed an augmentation of the defects. For patients with an intermediate probability of ACS (n = 14), four showed a positive rest MPI. On stress MPI, of these four cases, one showed no change from the rest MPI and three showed augmentation of defects. Of 10 negative cases on rest MPI, one patient remained negative on stress MPI and nine patients showed new perfusion defects.
Conclusion: MPI in the emergency department is feasible and useful in an emergency room to categorize patients with ACS into low- and high-risk groups. This can help in the proper management of ACS patients when other investigations are inconclusive.
Role of SPECT-CT in Radiotherapy
S. Sergieva, I. Mihailova, Z. Zahariev, M. Dimcheva
Department of Nuclear Medicine, Sofia Cancer Center, Sofia, Bulgaria
Abstract: The clinical application of fusion imaging methods, SPECT-CT and PET-CT, is currently being investigated in radiotherapy treatment planning. Up to date image-guided radiotherapy extensively involves computed tomography (CT) and magnetic resonance imaging (MRI) image data. The quality of target radiotherapy directly depends on the precise determination of:
SPECT and PET provide extra information for GTV delineation. The SPECT-CT modality is useful to visualize tumor tissues using different gamma-emitted radiopharmaceuticals. SPECT-CT allows correct localization of "hot" scintigraphic spots, differential diagnosis of physiological from pathological uptake, benign from malignant lesions and residual or recurrent tumor masses from the fibrous tissue after treatment. Several useful SPECT-CT clinical applications in radiotherapy planning including SLN mapping, tumorotropic scintigraphy with 99m Tc-MIBI/Tetrofosmin in breast cancer, thymoma, lung cancer, bone scintigraphy, somatostatin-receptor scintigraphy with 99m Tc-Tektrotyd and thyroid scintigraphy are considered. The received SPECT-CT date can modify GTV and influence the radiotherapy beam arrangement.
- The gross tumor volume (GTV) - macroscopic tumor tissue is based on imaging and histopathological modalities.
- The clinical target volume (CTV) - this volume includes GTV with margin, accounting for subclinical microscopic invasion, e.g. CTV = GTV + 0.5 cm. CTV is the anatomical-clinical volume.
- GTV and CTV are purely oncological concepts independent of any technology. The corresponding radiotherapy terms are Planning Risk Volume (PRV),/Gilbert Boisserie in ", Cancer Radiother": 2001 Nov; 5 Suppl 1:15s-35s.
- Planning target volume (PTV) - this volume includes CTV with a safety margin from organ motion, daily patient setup, radiation technique and intratreatment variation. PTV is a geometrical concept.
- The volume of the organ at risk - organs at risk have a tolerance dose that depends on the dose per fraction, but the dose must be kept as low as possible.
- Radiotherapy tools used in our study are as follows:
- Linear accelerator - Primus HE and Varian Clinac.
- Simulator and source projectors.
- Planning system, the multi-leaf collimators that allow the intensity modulation of the beam taking into account the heterogeneity of the tissues, the shapes of the body and the shape of the PTV.
- Portal imaging systems - allow verification of the treatment field accuracy produced by the treatment machine at the time of treatment.
Conclusion: The integration of modern multiple modalities such as SPECT-CT, PET-CT PET-MRI may allow identification of target and non-target structures using morphological, functional and biological information better than applying each single imaging modality.
The Association of HIV and Skeletal Metastases in Breast Cancer
Masha Maharaj, Nisaar Korowlay 1
Department of Nuclear Medicine, University of Limpopo, Polokwane Campus, South Africa, 1 Division of Nuclear Medicine, Tygerberg Hospital Stellenbosch University, South Africa
Aim of the Study: Skeletal involvement occurs in 30-70% of all cancer patients, with breast cancer being the leading cause for bone metastases in women and prostate cancer in men, followed by lung cancer. Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome. It is yet unknown as to what is the impact of HIV on the onset and progression of disease in breast cancer. The purpose of this study was to determine the association of HIV infection and skeletal metastases in breast cancer using skeletal scintigraphy.
Materials and Methods: This is a retrospective analysis. All bone scans performed at the Polokwane Provincial Hospital, Pietersburg, South Africa, were analyzed from January 2013 to July 2013. All patients in the study were female. The mean age of the patients was 46 years, with an age range of 28-62 years. Twenty-four bone scans were reviewed in the study: 12 patients who were HIV positive and 12 patients who were HIV negative, of similar age and similar histology, were compared.
Results: Of the 12 HIV-positive patients, only four showed skeletal metastases on bone scan. Skeletal metastases were seen in all 12 non-HIV patients.
Conclusion: From this small series, it appears that HIV prevents the progression of skeletal metastases in breast cancer.
Tc-99m MIBI Scintigraphy as an Early Predictor of Radioiodine Treatment Response in DTC
G. Gunawan, B. Hidayat, B. Darmawan, A. H. S. Kartamihardja, J. S. Masjhur
Department of Nuclear Medicine, Universitas Padjadjaran, Dr. Hasan Sadikin Hospital, Bandung, Indonesia
Aim of the Study: Stimulated serum thyroglobulin (Tg) level (TSHs >30 μIU) measurement 6 months post-radiothyroablation is the gold standard in evaluating radioiodine therapy response for differentiated thyroid cancer (DTC). The stimulated serum Tg level is achieved by withdraw levothyroxine 4-6 weeks after radioiodine therapy, which leads patients to a hypothyroid state. The Tc-99m MIBI uptake is not influenced by TSHs level and also can be used to identify and localize the DTC cell. Hence, the success of radiothyroablation can be performed earlier. The aim of this study was to assess Tc-99m MIBI 3 months after radiothyroablation as an initial predictor of radiothyroablation response.
Materials and Methods: Fifty-two DTC patients, 42 female (80.0%) and 10 male (19.2%), with a history of radiothyroablation 2 months before were enrolled in the study. Acquisition was performed 120 min after an intravenous injection of Tc-99m MIBI. The uptake ration was generated by dividing the uptake of the thyroid bed ROI with the background ROI. Correlation between Tc-99m MIBI scintigraphy and stimulated serum Tg level was calculated with a regression test. The Tc-99m MIBI uptake ratio was divided into two groups: Group I - negative uptake (1.29-1.35) of 45 (86.6%) subjects and group II - positive uptake (1.61-1.92) of seven (13.4%) subjects.
Results and Conclusion: There was a good correlation between Tc-99m MIBI scintigraphy and stimulated serum Tg level (r = 0.804 and P <0.0001). The cut-off point of the Tc-99m MIBI uptake ratio was 1.44, with a sensitivity of 87.5% and a specificity of 90.91%. It was concluded that there was a good correlation between Tc-99m MIBI scintigraphy and stimulated serum Tg level for radiothyroblation response.
SNOLL (Sentinel Lymph Node Biopsy and Radioguided Occult Lesion Localization) in Early Breast Carcinoma: A Two Years' Experience in Slovakia
L. Kaliska, M. Vereb, I. Miksikova, I. Turcan, J. Hanudel
INMM Banská Bystrica, PET centrum Agel Diagnostic, Banská Bystrica, Slovakia
Aim of the Study: The ROLL is a rather new technique applied for the localization of malignant impalpable (occult) breast lesions using the radiotracer instead of a standard surgical procedure with wire-guided localization (WGL). The so-called SNOLL procedure represents a combination of the ROLL technique with sentinel lymph node biopsy (SLNB), which are performed in a single surgical session. Several recently published studies have shown that the SNOLL procedure is reliable in localizing non-palpable breast lesions with a lower rate of re-excisions for positive margins compared with WGL. Our aim was to evaluate the efficacy of the SNOLL technique for the localization of malignant non-palpable breast lesions in a group of Slovakian women with early breast cancer.
Materials and Methods : Fifty-three patients with impalpable breast lesions underwent the ROLL procedure before breast-conserving surgery. An intratumoral injection of 0.2 mL of immobile radiotracer (10-150 μm particles of macro-aggregated albumin) labeled with 10 MBq of 99m Tc was applied 1-2 h before surgery under imaging guidance. Stereotactic mammography was used in 24 patients and 29 patients were managed under ultrasound guidance. Sentinel node localization was performed using 0.2 mL of the mobile radiotracer (100-600 nm particles of Sentiscint) labeled with 30-120 MBq of 99m Tc that was injected subdermally within the upper lateral quadrant of the breast periareolar area the morning or 1 day before the surgery (according to the 1-day or 2-day protocol). The sentinel lymph nodes were imaged by a gamma-camera using planar lymphoscintigraphy (LSG) in two projections. Breast-conserving surgery and SLN biopsy were performed during the same operation guided by a gamma probe.
Results : Breast lesions were localized by ROLL in 100% of the patients. Histological examination revealed negative margins in 86.8% of the cases. Sentinel lymph nodes were not detected by LSG in one case. Intraoperative SLN detection by gamma probe was successful for 98% of the SNOLL procedures.
Conclusion : In our experience, the SNOLL technique was effective and safe. The radiotracer-guided surgery showed a 100% localization rate for non-palpable breast lesions. Re-excision due to positive tissue margins was performed in 13.2% of the patients, which is comparable with the other published data in the literature. This rate demonstrates better results that are achieved with the standard WGL procedure. The localization rate for sentinel lymph nodes was 98%, which might also be considered as successful. An additional blue dye mapping might be used for patients with a negative drainage on LSG. According to our results, the SNOLL should be recommended as a standard procedure in the management of patients with non-palpable early breast cancer. In conclusion, we can state that nuclear medicine with the SNOLL procedure brought a new, possibly highly effective tool that might significantly contribute to the successful therapy of non-palpable breast carcinoma.
Breast Cancer and Autoimmune Thyroiditis: Does the Sodium Iodide Symporter Play a Role?
Jefferson R. Pagsisihan, Hyun-Yeol Nam, Jae Seon Eo, June-Key Chung, Dong Soo Lee
Department of Nuclear Medicine, Seoul National University Hospital, Seoul, South Korea
Aim of the Study: Breast cancer is the most common malignancy in women. Thyroid disease is likewise prevalent in the female population. On whole body PET/CT, increased thyroid gland uptake of F-18 Fluorodeoxyglucose (FDG) is sometimes encountered. It may appear to be diffusely or focally increased. Sodium iodide symporter is found in both the thyroid gland and in the breast. This study aims to determine the incidence and evaluate the clinical significance of diffusely increased thyroidal uptake of F-18 FDG in breast cancer patients. This study also aims to determine the possible role of NIS in thyroid disease among breast cancer patients.
Materials and Methods: The study population comprised of 440 adult female cancer patients. Those who were diagnosed with thyroid and ovarian malignancy as well as those with previous thyroid surgery were excluded from the study. Whole body PET/CT images and medical records were reviewed. The presence of NIS mRNA in the serum was determined using nested reverse transcriptase-polymerase chain reaction.
Results: One hundred and thirty-three (30.2%) patients had breast cancer while 307 (69.8%) patients had malignancies other than breast cancer. Diffusely increased thyroidal uptake was demonstrated in 18.8% and 10.4% patients in the breast cancer group and non-breast cancer group, respectively. There was a significant difference between these incidence rates. Diffusely increased thyroid uptake was more frequently noted in women aged ≥50 years old. The average SUVmax of the thyroid gland in breast cancer patients with diffusely increased thyroid uptake (3.33) was significantly higher than in those who did not exhibit increased thyroid uptake (1.25) (P <0.0001). In the patients with diffusely increased thyroid uptake, the average SUVmax of the thyroid gland of the non-breast cancer group (4.80) was significantly higher than that of the breast cancer group (3.33) (P = 0.021). There was no statistical significance in the incidence of diffusely increased thyroid uptake with regard to cancer stage and hormone receptor status. On further thyroid gland evaluation, autoimmune thyroditis was noted in the breast cancer patients with diffusely increased uptake. NIS mRNA was detected in the serum of the breast cancer patients and was negative in all the normal controls.
Conclusion: Diffusely increased thyroidal F-18 FDG uptake was more frequently exhibited in patients with breast cancer. Further thyroid gland evaluation revealed autoimmune thyroiditis. NIS mRNA was detected in the serum of the breast cancer patients. These are suggestive of an association between breast cancer and autoimmune thyroiditis and the possible role of NIS in the causation of this milder form of autoimmune thyroiditis.
Novel Method for Cyclotron Production of 45 Ti
M. Aboudzadeh, Y. Fazaeli, M. Aboudzadeh, G. Aslani, S. Moradkhani, K. Yousefi
Nuclear Medicine, Agricultural, Medical and Industrial Research School, Moazen Blvd., Karaj, Iran
In this study, after considering the excitation functions for 45 Sc (p, n) 45 Ti reaction using TALYS and ALICE/ASH codes and comparison with other experimental data, 45 Ti was produced by the dint of pressing method with a newly manufactured shuttle, and an experimental yield of 403.3 MBq/μAh was reported. Essential target thickness and physical yield were calculated by SRIM codes. The scandium oxide target was irradiated at 20 μA current and 21 MeV proton beam energy for 1 h and highly pure 45 Ti in the form of chloride was achieved. In this type of pressing method, any environmental contamination that may be produced in the sedimentation production method and some toxic elements due to the electroplating bathe in the electroplating production method do not exist. However, considering the ability to have a desirable beam current as well as lowering the risk of environmental pollution by shielding the target material into the capsule, this approach for targetry can be a suitable candidate for radiopharmaceutical productions.
Benign Lymphadenopathies on FDG PET/CT: Castleman's Disease, Kikuchi-Fujimoto's Disease and Reactive Lymph Node Hyperplasia
Jamilla Cecilia L. Gomez, Gerard F. L. Goco
Department of Nuclear Medicine, St. Luke's Medical Center, Quezon City, the Philippines
Benign lymphadenopathies on F- 18 fluorodeoxygloucose positron emission tomography-computed tomography (PET/CT) may demonstrate low-grade or high-grade FDG avidity. In this case series, we describe the utility of PET/ CT in various cases of lymphadenopathies that one should be recognizant of when encountering them. PET/CT has been known to improve lymphoma staging by detecting lymphoma nodal sites more accurately than CT. The FDG activity of lymph nodes is considered to be of low FDG uptake if it is comparable to that of the mediastinum. One of the patients was diagnosed with undifferentiated connective tissue disease but with multiple lymphadenopathies. Lymph nodes on PET/CT showed low-grade uptake thus excluding malignancy such as lymphoma. Lymph node histopathology confirmed this as Castleman's disease. Lymphoma was only excluded through PET/CT. PET/CT can therefore be utilized to differentiate benign lymphoproliferative diseases such as Castleman's disease from conditions with higher metabolic FDG uptake such as malignant lymphoma. On the other hand, increased FDG activity in enlarged lymph nodes does not always point to malignancy. In this case series, we describe patients with breast carcinoma and retroperitoneal liposarcoma, both with multiple lymphadenopathies that are FDG-avid on PET/CT. These turned out to be Kikuchi-Fujimoto's lymphadenopathy and reactive lymph node hyperplasia, respectively. FDG could accumulate in the inflamed/reactive lymph nodes and benign lymphoproliferative disorders such as Kikuchi-Fujimoto's disease with no malignant potential. These can be misinterpreted as malignancy/metastases. Knowledge of these cases will be beneficial when interpreting lymphadenopathy on PET/CT.
Outcome of Radioiodine Therapy in Benign Nodular Non-Toxic Goiter: A Preliminary Study
Karina Michaela Dela Cruz, Jasmine De Jesus, Juan Torres
University of Santo Tomas Hospital, Manila, the Philippines
Aim of the Study: Goiter is a common condition in countries where low iodine intake is still a problem. For the past 20 years, radioiodine therapy has been used for treating goiter. It is a non-invasive, safe and cost-effective method of therapy that results in a significant reduction in thyroid volume. This study will investigate the efficacy of I-131 treatment on thyroid function and size reduction in a group of patients with scintigraphic findings of nodular goiter.
Materials and Methods: This is a prospective study of patients with nodular goiter selected for radioactive iodine therapy in a tertiary hospital from 2011 to 2012. All participating patients underwent both pre- and post- RAI therapy I-131 thyroid scans and serum concentration of thyroid stimulating hormone.
Results: A total of 40 patients were included in this study, comprising 35 females and five males with a mean age of 42.48 ± 15.33 years. The mean TSH pre-therapy was 1.97 ± 6.53 mIU/mL. The mean dose of RAI given was 6.53 ± 1.64. The mean follow-up interval was approximately 3-6 months. The mean thyroid volume pre-treatment was 41.26 ± 12.02 cm 3 compared with 31.82 ± 9.46 cm 3 post-treatment, with a percent reduction of 17.28 ± 16.31 cm 3 . The mean nodule size pre-treatment was 6.51 ± 4.79 cm 2 compared with 2.66 ± 3.52 cm 2 post-treatment, with a percent reduction of 71.39 ± 32.59 cm 2 . In a significant number of patients, there was a complete disappearance of the nodules. There was clinical improvement of previously noted anterior neck enlargement and obstructive symptoms. There was no increase in the thyroid size or development of new nodules or worsening of obstructive symptoms noted at the end of the study.
Conclusion: Radioactive iodine therapy is an effective, non-invasive and safe management that could be used as a primary therapy in patients with benign nodular non-toxic goiter.
Pleuro-Peritoneal Communication Detected by Technetium 99m-Tagged Macroaggregated Albumin Radionuclide Peritoneal Scintigraphy in a Chronic Kidney Disease Patient on Peritoneal Dialysis
Carla Mari M. Macaisa, Raymund Augustus O. Conlu, Joe Ryan A. Agga, Karina Michaela D. Del Mundo, Oliver R. Lubiano
This case will present the value of peritoneal scintigraphy in evaluating the pleuroperitoneal communication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). End-stage renal disease (ESRD) is one of the leading causes of mortality in the Philippines. The rise of ESRD coincides with an increase in the number of patients with diabetes mellitus and hypertension in the past few decades. ESRD patients either undergo peritoneal dialysis or hemodialysis. CAPD has found a 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. Determining the site of origin of the fluid is necessary for planning the treatment when complications are encountered. This case presents the value of peritoneal scintigraphy in evaluating pleuroperitoneal communication in patients undergoing CAPD. This is a case of an 83-year-old female diagnosed with chronic kidney disease secondary to hypertensive nephrocalcinosis, who presented with sudden-onset dyspnea and tachypnea after her first peritoneal dialysis. She was referred for peritoneal scintigraphy to detect any possible pleuroperitoneal leak. Peritoneal scintigraphy was performed after intravenous administration of 185 MBq of Tc-99m MAA in 1 L of peritoneal dialysis fluid. Beginning on the fifth minute of the study, a faint blush of activity was seen arising from the upper portion of the right hemiabdomen into the right hemithorax. 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 hemithorax throughout the duration of the study. This confirmed the suspected pleuroperitoneal communication in the right hemithorax, 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 pleuroperitoneal communication. It may play an important part in decision-making for patients on peritoneal dialysis with a suspicion of pleuroperitoneal leak.
Pre-Clinical Dosimetry and Prognosis of the Safety and Effectiveness of Radiopharmaceuticals 188 Re-Zoledronic Acid
L. V. Voloznev, A. S. Lunev, O. E. Klementyeva 1 , V. N. Korsunsky 1
Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Russia, 1 Burnasyan Federal Medical Biophysical Center, Moscow, Russia
Aim of the Study: There is a necessity of knowledge about created absorbed doses in tumors, organs, tissues and the whole organism for prognosis of the safety and efficiency of the new radiopharmaceuticals before their first application to mankind. The information gathered during the pre-clinical studies of dosimetry is aimed to make a decision as to whether clinical trials of radiopharmaceuticals are possible or not. This information is necessary to estimate the probable toxicity and effectiveness and to calculate the "risk-benefit" ratio.
Materials and Methods: All animal experiments were carried out according to the principles of laboratory animal care. For calculation of the absorbed doses, we used data about 188 Re-zoledronic acid biodistribution. 188 Re-zoledronic acid (1.2 mCi/kg) was injected into the tail veins of rats; then, after 1, 3, 5, 24 and 48 h, the samples of the organs, tissues and callus (model of metastasis) were taken for evaluation of biodistribution (radiometry, γ-counter Wizard 2480). The model of bone metastasis was simulated via tibia fracture (callus). The data about biodistribution of 188 Re-zoledronic acid were extrapolated to human organisms by Kirschner's formula (Kirschner et al., 1975). The absorbed doses of 188 Re-zoledronic acid in some organs and tissues were calculated using the application OLINDA/EXM 1.0 (Stabin et al., 2005). The "benefit-risk" ratio (Κb/r ) was calculated as K b/r = D met /D rm ; D met - average absorbed dose of metastasis, D RM - absorbed dose of red marrow.
Results: The effective dose for the whole organism was calculated throughout the series of the experiments. The effective dose for 188 Re-zoledronic acid is 0.48 Sv (0.154 mSv/MBq for injected activity 45 MBq/kg, weight 70 kg). It fits the requirements of UNSCEAR. The largest absorbed doses were registered in the urinary bladder: 4.33 Gy, skeleton: 2.89 Gy and kidneys: 1.65 Gy. This is due to the bone-seeking biodistribution of 188 Re-zoledronic acid and its intensive breeding through the urinary system. The listed doses were less than the maximum allowable value, which equals 10 Gy. The absorbed dose in the red marrow, 0.23 Gy, was more than 10-times less than the maximum allowable value (2.5 Gy). The absorbed dose in the pathological area (metastatic model) was 10.2-49.9 Gy (7.8 ± 5.3 mGy/MBq). The "benefit-risk" ratio equaled 100.0. The ratio and the absorbed doses allow one to achieve a stable palliative effect and a low risk of potential side-effects.
Conclusion: The results of the pre-clinical predictable dosimetry of 188 Re-zoledronic acid claim the high effectiveness of palliative therapy of metastatic bone disease and the low risk of toxicity.
The Role of 99m Tc Hydroxydiphosphonate Scintimammography in the Diagnosis of Breast Cancer
Chris Eduarte, Bonan Achilles Mendoza
Nuclear Medicine, Jose Reyes Memorial Medical Center Manila, the Philippines
Aim of the Study: Mammography, physical examination and 99m Tc Sestamibi scintimammography are currently the most frequent and recognized screening tools for the detection of breast carcinoma. The aim of this study is to determine the sensitivity, specificity, accuracy and positive and negative predictive values of an alternative radiopharmaceutical, 99m Tc HDP, in the diagnosis of malignant breast lesions.
Materials and Methods: A total of 53 women aged between 19 and 60 years (mean: 39.5 years) with suspected breast lesions detected by palpation that require fine needle aspiration/excision biopsy were included in the study after randomization. The histopathological result of the biopsy or surgery was used as the gold standard to determine the accuracy, sensitivity, specificity and both positive and negative predictive value.
Results: The histopathologic samples obtained from mastectomy or excision biopsy led to a diagnosis of malignancy in 21 of 53 lesions. Four different histologic types of malignant tumors were identified. 99m Tc HDP scintimammography diagnosed 18 malignant lesions correctly. There were three breast cancers that were false negative on scintimammography (<2 cm). False-positive uptake of 99m Tc HDP was seen in one lesion.
Conclusion: This study confirms that 99m Tc HDP scintimammography is potentially useful in differentiating breast cancer from benign tumor. It has an accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 92.45%, 85.7%, 96.8%, 94.7% and 91.2%, respectively.
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