SBIR-STTR Award

Boron Neutron Capture Therapy is currently in clinical trials for the treatment of Glioblastoma Multiforme brain tumors and multiple metastatic melanoma. The technique relies on the deposition of a boron-containing agent in tumors. The current agent is not sufficiently selective in the cancers being treated. This proposal is focused on the preparation (Phases I and II) and the testing (Phase II) of a promising new series of boronated amino acids. Based on preliminary nuclear medicine data, the new boronated agents should more effectively deposit in tumors. A series of new unnatural boronated, cyclic amino acids will be prepared. The materials are analogues of nuclear medicine agents that are known to localize in tumors.

Commercial Applications and Other Benefits as described by the awardee:
The successful development of tumor-selective boronated agents will improve the efficiency of Neutron Capture Therapy and permit the therapy to move to the commercial arena. BioNeutrics is in the process of modifying the Tower Shielding Reactor on the Oak Ridge National Laboratory reservation for commercial neutron therapy application.

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.