Sweet Battle of the Epimers─Continued Exploration of Monosaccharide-Derived Delivery Agents for Boron Neutron Capture Therapy

Abstract

Boron neutron capture therapy (BNCT) is a cancer therapy in which boron delivery agents play a crucial role. In theory, delivery agents with high tumor targeting capabilities can lead to selective eradication of tumor cells without causing harmful side effects. We have been working on a GLUT1-targeting strategy to BNCT for a number of years and found multiple promising hit compounds which outperform the clinically employed boron delivery agents in vitro. Herein, we continue our work in the field by further diversification of the carbohydrate scaffold in order to map the optimal stereochemistry of the carbohydrate core. In the sweet battle of the epimers, carborane-bearing D-galactose, D-mannose, and D-allose are synthesized and subjected to in vitro profiling studies�with earlier work on D-glucose serving as the reference. We find that all of the monosaccharide delivery agents display a significantly improved boron delivery capacity over the delivery agents approved for clinical use in vitro, thus providing a sound foundation for advancing toward in vivo preclinical assessment studies.

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

“…Despite the great effort reported in the literature regarding the synthesis and in vitro testing of carbohydrate derivatives of carboranes [73,[79][80][81][82], the examples of such compounds tested in vivo are few [83][84][85][86]. Ortho-carboranyl glycosides of glucose, maltose and lactose were synthetized and tested in vitro for their toxicity toward C-6 rat glioma cells after thermal neutron treatment [87], but only the carboranyl maltoside compound was tested in vivo [88].…”