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3rd International Congress 3rd International of Nuclear Congress Medicine of Nuclear & 15th Medicine Iranian Annual & 15th Iranian Congress Annual of Nuclear Congress Medicine of Nuclear Medicine Shahid Beheshti Shahid Beheshti University University of Medical Sciences of Medical 19-21 Sciences May 201119-21 May 2011 Production, Quality Control and Biological Evaluation of 153Sm-TTHMP as a Possible Bone Palliation Agent Zohre Naseri 1 , Amir Reza Jalilian 2 , Ali Nemati Kharat 1 1 University of Tehran, School of Chemistry 2 Radiopharmaceutical Research and Development Lab (RRDL) Radionuclides have been used to treat skeletal diseases for decades. At present an array of radionuclides have been proposed for treating bone pain due to cancer. The most promising among these radionuclides is 153Sm. This radionuclide has favourable radition characteristics t1/2= 1.93d, βmax= 0.81 Mev(20%), 0.71 Mev (49%), 0.64 Mev (30%) and γ=103 Kev (30%) emission which is suitable for imaging purposes during therapy. Various bone palliative therapeutic agents have been developed for bone metastasis such as 153Sm-EDTMP, widely used in the world. (EDTMP) has been proved to be a good therapeutic agent for the treatment of pain due to skeletal metastases and is now commercialized. In this study, production, quality control and biodistribution studies of a newly developed therapeutic compound have been presented followed by imaging studies in wild-type rodents. 153Sm-TTHMP was prepared starting 153Sm-SmCl3, prepared by neutron activation of an enriched 152Sm sample (purity >98%), and in-house synthesized TTHMP in 1h at 25ºC followed by stability tests, partition coefficient determination and biodistribution studies of in wild-type rodents using scarification. The radiolabeled Sm complex was prepared in high radiochemical purity (>99%, ITLC) and specific activity of 278 GBq/mmol and demonstrated significant stability at 4, 25 and 37ºC (in presence of human serum). Initial biodistribution data showed significant bone accumulation of the tracer in 48h. The produced 153Sm-TTHMP properties suggest an efficiently new bone palliative therapeutic agent in the country in order to overcome the metastatic bone pains. Keywords: Sm-153, TTHMP, Radiopharmaceutical, Therapy, Biodistribution, Imaging 82
3rd International Congress of of Nuclear Medicine & & 15th 15th Iranian Annual Annual Congress of Congress of Nuclear Medicine Shahid Beheshti Shahid Beheshti University University of Medical of Medical Sciences Sciences 19-21 19-21 May May 2011 Preparation and bio distribution of 99m Technetium-annexin V for in vivo detection of apoptosis Saeed Rajabifar, Hamidreza Zolata, Fateme Bolourinovin, Fariba Sadadi, Amir Reza Jalilian Nuclear Medicine group, Agricultural,Medicl and Industrial Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran. Introduction: Annexin V a human protein belongs to a class of Ca 2+ -dependent binding proteins and has a high affinity for phosphotydilserine and can be used in determination of apoptosis in cells. Annexin V and its conjugates may be used to detect apoptotic cells significantly earlier than DNA- based assays. Labeled Annexin V using 99m Technetium may be useful in detection of apoptosis in vivo as well as effects of the drugs used for the therapy. Methods and material: For radiolabeling of Annexin V with 99m technetium succinic dihydrazide, propylene diamine tetra acetic acid, tricine, nicotinic acid and stannous chloride at their best concentrations in 0.1 M hydro chloric acid were added to phosphate buffer at PH=8.5 and then 110 MBq 99m technetium eluted by normal saline and Annexin V were added to this mixture and heated at 90 oc for 10 minutes using stirrer at 1400 rpm. The radiochemical purity of 99m technetium was determined by ascending Instant Thin Layer Chromatography (ITLC) with silica gel fiber glass sheet. Two solvents such as physiologic saline and acidified 85% ethanol were used and compared. The radiopharmaceutical prepared was administered through tail vein to experimental animals (n=5) and under anesthesia sacrificed for bio distribution studies at 1 and 3 hrs. Liver, kidney, heart, muscle, spleen, stomach, and intestine. Results: The radio chemical purity was found to be not less than 90% and the ethanol solvent showed better results as compare to the normal saline. The serum stability studies showed the product is stable at least up to 1 hr. The highest percentage of injected dose per gram of organ (%ID/g) with the mean value were observed in liver 2.56, kidney 1.36, heart 0.53, stomach 0.39, spleen 0.37 and muscle 0.12 . Appreciable radio activity could be detected in the liver and kidneys until 3 hrs post injection of 99m technetium- Annexin V indicating radiopharmaceutical primarily excretion by hepatic and renal pathway. Stomach uptake is commonly assumed as a control of 99m technetium labeled compounds stability in vivo assays, this tissue actively uptakes free 99m technetium which is a good indicator of radiochemical purity. Conclusion: 99m technetium-Annexin V is successfully labeled and the highest uptake was observed in liver and kidney. Stomach uptake of 99mTc labeled Annexin was negligible ,confirming no contamination of free 99m technetium in the preparation. Keywords:AnnexinV,Apoptosis, 99m technetium-AnnexinV, Labeling 83
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