Synthesis and Evaluation of Amine Reactive Carboranyl Derivatives for Application to Boron-10 Containing Polymers

The use of monoclonal antibodies to selectively deliver boron-10 to cancer cells for boron neutron capture therapy (BNCT) has been under active investigation for over 20 years (1). A major difficulty in the application of boronated antibodies is the high concentrations of boron-10 required in the tumor tissue (e.g. 35 mg B-10/g tissue) (2). Simple calculations have shown that each antibody molecule must have a minimum of 600–1000 boron atoms to achieve the concentrations of boron-10 required (1-4). Seemingly, the only way to achieve such a large number of boron atoms per antibody molecule is to incorporate the boron into a polymer, then attach the boronated polymer to the antibody. Further, the coupling of boron containing polymer with the antibody must be accomplished in a manner that does not adversely affect its antigen binding or dramatically change the physical properties of the antibody (e.g. net ionic charge). Thus, it seems that a reasonable objective would be to prepare a neutral boronated polymer which could be site-specifically attached to the antibody.