Boron Neutron Capture Therapy (BNCT) is a very promising therapy for certain tumors, such as gliomas and melanomas. p-Boronophenylalanine (BPA), an analog of phenylalanine, is one of the leading BNCT agents and is currently undergoing clinical trials in the U.S. for the treatment of gliomas and melanomas. It has already been used clinically in Japan for the treatment of melanoma. Although very effective, a major drawback of BPA is the high dose of compound required to achieve clinically effective concentration of boron- 10 in the tumor. It would be quite advantageous to design new BPA analogs that retain the physico-chemical and bio-distribution properties of BPA, yet have higher boron content. The Phase I studies are therefore designed to synthesize analogs of BPA with high boron content and different polar functional groups. The high boron content will allow the use of smaller quantities of BNCT agents, while the polar functional group provides a handle to control the physico-chemical properties to optimize the structure for best tumor uptake and selectivity. The phase I studies will also evaluate the in vitro cell uptake and biological efficacy for BNCT. Phase II research will focus on further structure optimization and in vivo BNCT efficacy and toxicological studies.
