Boron Neutron Capture Therapy (BNCT) has a clear theoretical advantage over other techniques as a method of delivering cell-killing radiation to tumors. The inability of leukemia cells to synthesize asparagine and the requirement of exogeneous asparagine by tumor cells provide an excellent opportunity for exploitation by BNCT, using boron analogs. Boronic acids are also good inhibitors of serine proteases and good analogs of transition states in enzymatic reactions, Boron-containing transition state analogs of asparagine and glutamine could use the inhibition mechanism to control tumor proliferation. Incorporation of boron into tumor cell can pave way for cell destruction by BNCT. Phase I research will focus on the synthesis of (i) boron-containing transition state analogs of asparagine and glutamine, (ii) a delta- boronated amino acid, and evaluation of their cytotoxicity and in vitro efficacy. Phase II effort will focus on (i) synthesis of other boronated amino acid analogs and their peptides, (ii) further in vitro toxicity, in vivo efficacy studies, and (iii) BNCT, antineoplastic activity and long term toxicity of lead compounds.
