New Synthetic Strategy of MRI/BNCT Agents Based on Hydroboration Reaction

Boron neutron capture therapy (BNCT) is a binary strategy for cancer treatment based on nuclear 10B interaction with a thermal neutron flow, which requires the introduction within cancer cells of 15-30 µg B per gr of tumor tissue with high selectivity. These B amounts are necessary for an efficient treatment, while a selective introduction in tumor preserves other cells from damages. Another aspect is the importance of following in vivo 10B distribution to check the tumor position. Decaboranes show good in vivo stability and powerful versatility. In this work a new synthetic strategy, based on carborane hydroboration reaction, is reported. Starting from B-substituted alkyldecaboranes, dehydrogenative insertion reaction with terminal alkynes allows functionalized dicarba-closo-dodecaboranes to be synthetized. On one side the carborane cage has been functionalized with a lipophilic moiety by hydroboration reaction in order to allow the interaction with LDLs or liposomes (the real biological vectors). On the other side the carborane cage has been functionalized by dehydrogenative insertion reaction with a terminal alkyne, subsequently linked to a Gd-DOTA complex as MRI probe.