Boron neutron capture therapy of brain tumors: An emerging therapeutic modality

BORON NEUTRON CAPTURE therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, a stable isotope, is irradiated with low-energy therm al neutrons to yield alpha particles and recoiling lithium-7 nuclei. For BN CT to be successful, a large number of B-10 atoms must be localized on or p referably within neoplastic cells, and a sufficient number of thermal neutr ons must be absorbed by the B-10 atoms to sustain a lethal B-10 (n, alpha) lithium-7 reaction. There is a growing interest in using BNCT in combinatio n with surgery to treat patients with high-grade gliomas and possibly metas tatic brain tumors. The present review covers the biological and radiobiolo gical considerations on which BNCT is based, boron-containing low- and high -molecular weight delivery agents, neutron sources, clinical studies, and f uture areas of research. Two boron compounds currently are being used clini cally, sodium borocaptate and boronophenylalanine, and a number of new deli very agents are under investigation, including boronated porphyrins, nucleo sides, amino acids, polyamines, monoclonal and bispecific antibodies, lipos omes, and epidermal growth factor. These are discussed, as is optimization of their delivery. Nuclear reactors currently are the only source of neutro ns for BNCT, and the fission reaction within the core produces a mixture of lower energy thermal and epithermal neutrons, fast or high-energy neutrons , and gamma-rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epith ermal neutron beams now are being used in the United States and Europe beca use of their superior tissue-penetrating properties. Currently, there are c linical trials in progress in the United States, Europe, and Japan using a combination of debulking surgery and then BNCT to treat patients with gliob lastomas. The American and European studies are Phase I trials using borono phenylalanine and sodium borocaptate, respectively, as capture agents, and the Japanese trial is a Phase II study. Boron compound and neutron dose esc alation studies are planned, and these could lead to Phase II and possibly to randomized Phase III clinical trials that should provide data regarding therapeutic efficacy.