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

ABSTRACT

Due to the anti-proliferative properties of platinum group-thiosemicarbazone complexes, the production of [191]Os-labeled 2-acetyl pyridine 4-N-methylthiosemicarbazone [[191]Os-APMTS] was investigated. [[191]Osmium [T[1/2]= 15.4d] was produced via the [190]Os[n,gamma][191]Os nuclear reaction using enriched target irradiated with thermal neutrons. Reaction of in-house synthesized 2-acetylpyridine thiosemicarbazone [APMTS] with [191]Os yielded [[191]Os]APMTS checked by ITLC followed by stability, partition co-efficient and biodistribution determination. 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[degree sign]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. 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