New Boronated Amino Acids for Neutron Capture Therapy

60076 Boron Neutron Capture Therapy (BNCT), used for cancer treatment, is in need of new and improved boron containing drugs that have been shown to accumulate in tumors (Glioblastoma melanoma, etc.) and not in surrounding tissue. This project will examine the extent to which a family of boron-containing cyclic amino acids are taken up by tumors and evaluate their promise as agents for use in clinical BNCT. In Phase I, a series of new tumor seeking unnatural cyclic amino acids were designed, and two were prepared. The materials were tested for toxicity in Balb/c mice and were found to be non-toxic. One of the new boronated amino acids was used in a biodistribution study involving Balb/c mice bearing EMT-6 tumors on their dorsal hip area. The results demonstrated that the reagent was taken up by the tumor while rapidly clearing from the blood. Based on the selectivity of the first compound prepared in the new family of water soluble cyclic amino acids, a series of boronated unnatural amino acids will be prepared in Phase II, varying the position and chemical type of the boron. These new boronated pharmaceuticals will be evaluated for tumor specificity using immune deficient mice bearing implanted tumors. The materials will also be screened for toxicity. Commercial Applications and Other Benefits as described by the awardee: If the tumor selectively of the new synthesized compounds is shown to be significantly higher than currently used BNCT compouds, there would be a new worldwide movement to utilize BNCT. Given new facilities around the world for treatment, the commercialization opportunities of these compounds should be significant.