Development and biological evaluation of Y-90-BPAMD as a novel bone seeking therapeutic agent

摘要

Nowadays, the bone-seeking radiopharma-ceuticals play an important role in the treatment of the bone-related pathologies. Whereas various phosphonate ligands have already been identified, a DOTA-based bisphosphonate, 4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl (BPAMD) with better characteristics has recently been synthesized. In this study, Y-90-BPAMD was developed with radiochemical purity > 98% and the specific activity of 3.52 TBq/mmol in the optimized conditions as a new bone-seeking therapeutic agent. The complex demonstrated significant stability at room temperature and in human serum even after 48 h. At even low amount of hydroxyapatite (5 mg), more than 90% binding to hydroxyapatite was observed. Biodistribution studies after injection of the complex into the Syrian rats showed major accumulation of the labelled compound in the bone tissue and an insignificant uptake in the other organs all the times after injection. Generally, Y-90-BPAMD demonstrated interesting characteristics compared to the other Y-90-bone-seeking agents and even Ho-166-BPAMD, and can be considered as a new bone-seeking candidate for therapeutic applications.