Radiosynthesis of 191Os-2-acetylpyridine thiosemicarbazone complex, as an in vivo therapeutic radionuclide generator

Introduction: Due to the anti-proliferative properties of platinum group-thiosemicarbazone complexes, the production of 191Os-labeled 2-acetyl pyridine 4-N-methylthiosemicarbazone (191Os-APMTS) was investigated. Methods: [191Osmium (T½= 15.4d) was produced via the 190Os(n,γ)191Os nuclear reaction using enriched target irradiated with thermal neutrons. Reaction of in-house synthesized 2-acetylpyridine thiosemicarbazone (APMTS) with 191Os yielded [191Os]APMTS checked by ITLC followed by stability, partition co-efficient and biodistribution determination. Results: Following synthesis and spectroscopic determination of the ligand (> 99% chemical purity), the complex was prepared with a radiochemical purity of more than 95% (RTLC) and specific activity of 21.5 GB/mM and was stable in the formulation and presence of human serum at 37°C for up to 48h. The partition coefficient was determined (log P. 1.23). The biodistribution study up to 4 days demonstrated significant tissue uptake differences in the bone, blood, heart and thyroid. Conclusion: This is the first Os-191 labeled thiosemicarbazone designed as an in-vivo therapeutic radionuclide generator. Further investigation is ongoing on the evaluation of the complex in tumor bearing animals.

Keywords:

Thiosemicarbazone , 191Os , Radiolabeling , Biodistribution