In Vivo Application of Carboranes for Boron Neutron Capture Therapy (BNCT): Structure, Formulation and Analytical Methods for Detection

Abstract

Carboranes have emerged as one of the most promising boron agents in boron neutron capture therapy (BNCT). In this context, in vivo studies are particularly relevant, since they provide qualitative and quantitative information about the biodistribution of these molecules, which is of the utmost importance to determine the efficacy of BNCT, defining their localization and (bio)accumulation, as well as their pharmacokinetics and pharmacodynamics. First, we gathered a detailed list of the carboranes used for in vivo studies, considering the synthesis of carborane derivatives or the use of delivery system such as liposomes, micelles and nanoparticles. Then, the formulation employed and the cancer model used in each of these studies were identified. Finally, we examined the analytical aspects concerning carborane detection, identifying the main methodologies applied in the literature for ex vivo and in vivo analysis. The present work aims to identify the current strengths and weakness of the use of carboranes in BNCT, establishing the bottlenecks and the best strategies for future applications.

Metallacarboranes in Medicinal Chemistry: Current Advances and Future Perspectives

“…Unfortunately, presented compounds still fail to fulfill all of the requirements listed for the ideal boron carrier in the BNCT treatment: they have insufficient cellular uptake and poor selectivity for cancerous over healthy cells, thus the search for novel and improved compounds still continues. At the very forefront of this hunt are various derivatives of carborane (C 2 B 10 H 12 ) and dodecaborate ([B 12 H 12 ] 2– ) molecules described in detail in many recent reviews − and books. − As rich boron atoms’ sources these 12-vertex boron cages are often attached to other molecules creating boronated polyamines, − amino acids, nucleic acids and nucleosides, carbohydrates, porphyrins, − phthalocyanines, , liposomes, , dendrimers, − and nanotubes . However, other auspicious candidates for bridging this gap are metallacarboranes (with [COSAN] − in particular), which possess a few characteristics (described in detail in the next chapters) underlying their utility as the 10 B source for neutron irradiation such as ability to cross cellular membranes without their disruption, accumulation inside nucleus and no apparent cytotoxicity.…”