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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 Synthesis, Radiolabeling and Biological Evaluation of [67Ga]- maltolate complex as an imaging agent Seyed Yousef Fazaeli 1 , Amir Reza Jalilian 1 , Mostafa M. Amini 2 , Abbas Majdabadi 1 , Ali Rahiminejad 1 , Fatemeh Bolourinovin 1 , Mehraban Pouladi 1 1 Nuclear Science and Technology Research Institute (NSTRI) 2 Department of Chemistry INTRODUCTION: The interesting physical properties and availability of gallium-67 make it an interesting nuclide for radiopharmaceutical research [1] recently. Studies of gallium maltolate as a potential treatment for liver cancer and gastrointestinal cancers has been done [2]. Gallium maltolate is stable in aqueous solutions between about pH 5 and 8, and it has significant solubility in both water and lipids.In this work we report, synthesis, radiolabeling, partition coefficient, quality control and biodistribution studies (using SPECT and scarification) of 67Ga-maltolate in Swiss mice.The time/activity diagrams for the labeled compound in vital organs have been plotted compared to gallium cation. METHODS [67Ga] labeled 3-hydroxy-2- methyl-4H-pyran-4-onate ([67Ga]- maltolate) was prepared using freshly prepared [67Ga]GaCl3 and 3-hydroxy-2-methyl-4H-pyran-4- onate in a sodium salt form for 25 min at 40°C (radiochemical purity: >96% ITLC, >98% HPLC, specific activity: 13-17 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 24 h. The partition coefficient was calculated for the compound (log P=0.40). The biodistribution of the labeled compound in vital organs of Swiss mice studied using scarification studies and SPECT imaging up to 24 h. A detailed comparative pharmacokinetic study performed for 67Ga cation and [67Ga]-maltolate. Results Total labeling and formulation of [67Ga]-maltolate took about 30 min. The complex was stable in final formulation and human serum at least for 24 h. At the pH.7, the logP was 0.4. The biodistribution of the labeled compound in vital organs of Swiss mice was studied using scarification studies and SPECT imaging up to 24 h. Conclusion It is suggested that [67Ga]-maltolate could be a possible SPECT tracer, however considering the fast wash-out and the short half life gallium- 68, [67Ga]-maltolate can be a suitable candidate for tumor imaging applications and future 68Ga-PET studies and less use and therefore less imposed radiation doses to patients. References: 1. R.B. Firestone, In: Table of isotopes. 8th edition, John Wiley and Sons, p.1447, New York, (1996). 2. C.R. Chitambar, "Development of Gallium Compounds for Treatment of Lymphoma: Gallium Maltolate. J. Pharmacol. Exp. Ther. (2007) 322. Keywords: ([67Ga]- maltolate), imaging agents, biodistribution 186
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 biological evaluation of radiogallium-labeled folate-embedded superparamagnetic nanoparticles in fibrosarcoma-bearing rat Seyydeh Leila Hosseini Salekdeh 1 , Amir Reza Jalilian 2 , Morteza Mahmoudi 3 , Hassan Yousefnia 2 , Majid Pouladian 1 1 Nuclear Engineering Departmant 2 Radiopharmaceutical Research and Development Lab (RRDL) 3 Institute for Nanoscience and Nanotechnology The development of a large variety of colloidal dispersions of super paramagnetic iron oxide nanoparticles (SPION) has added a supplementary function to nanomaterials, their magnetic properties, which led to a range of new biological and biomedical (diagnostic and treatment) applications. The interesting biological activity of folic acid as well as amphiphilic properties of this important hematopoietic vitamin was considered to be a multi-purposes functional additive to SPION core. Superparamagnetic iron oxide nanoparticles (SPION) embedded by folic acid (SPION-folate) were prepared by a modified co-precipitation method. The structure, size, morphology, magnetic property and relaxivity of the SPION-folate were characterized systematically by means of XRD, VSM, HRSEM and TEM and the interaction between folate and iron oxide (Fe3O4) was characterized by FT-IR. The particle size was shown to be ≈ 5-10 nm. Stability of 67Ga-SPION-folate in final preparation was determined by storing the final solution at 25C for 4 days and performing frequent ITLC analysis to determine radiochemical purity. Biocompatibility of the compound was investigated using an MTT assay followed by stability tests and tumor accumulation studies in fibrosarcoma-bearing mice after subcutaneous (s.c.) application. [67Ga]-SPION-folate (radiochemical purity> 96%, RTLC method) was evaluated in fibrosarcoma-bearing rat after subcutaneous injection. All values were expressed as mean ± standard deviation (mean ± SD) and the data were compared using student T test. Statistical significance was defined as P
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