Carborane derivative development for boron neutron capture therapy. Final report

Boron Neutron Capture Therapy [BNCT] is a binary method of cancer therapy based on the capture of neutrons by a boron-10 atom [10B]. Cytotoxic 7Li nuclei and α-particles are emitted, with a range in tissue of 9 and 5 microm, respectively, about one cell diameter. The major obstacle to clinically viable BNCT is the selective localization of 5-30 ppm 10B in tumor cells required for effective therapy. A promising approach to BNCT is based on hydrophilic boron-rich oligomeric phosphate diesters, or ''trailers'' that have been shown to concentrate selectively in tumor tissue. Examples of these compounds were prepared previously at high cost using an automated DNA synthesizer. Direct synthesis methods are needed for the production of gram-scale quantities for further biological evaluation. The work accomplished as a result of the collaboration between Fluorochem, Inc. and UCLA demonstrates that short oligomers containing at least five carborane units with four phosphodiester linkages can be prepared in substantial quantities. This work was accomplished by the application of standard phosphoramidite coupling chemistry