BORON NEUTRON-CAPTURE THERAPY OF BRAIN-TUMORS - PAST HISTORY, CURRENTSTATUS, AND FUTURE POTENTIAL

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradicated with low-energy thermal neutr ons to yield alpha particles and recoiling lithium-7 nuclei. High-grad e astrocytomas, glioblastoma multiforme, and metastatic brain tumors c onstitute a major group of neoplasms for which there is no effective t reatment. There is growing interest in using BNCT in combination with surgery to treat patients with primary, and possibly metastatic brain tumors. For BNCT to be successful, a large number of B-10 atoms must b e localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must reach and be absorbed by the B-10 ato ms to sustain a lethal B-10(n,alpha) Li-7 reaction. Two major question s will be addressed in this review. First, how van a large number of B -10 atoms be delivered selectively to cancer cells? Second, how can a high fluence of neutrons be delivered to the tumor? Two boron compound s currently are being used clinically, sodium borocaptate (BSH) and bo ronophenylalanine (BPA), and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino aci ds, polyamines, monoclonal and bispecific antibodies, liposomes, and e pidermal growth factor. There will be discussed, and potential problem s associated with their use as boron delivery agents will be considere d. Nuclear reactors, currently, are the only source of neutrons for BN CT, and the fission process within the core produces a mixture of lowe r-energy thermal and epithermal neutrons, fast ol high (>10,000 eV) en ergy neutrons, and gamma rays. Although thermal neutron beams have bee n used clinically in Japan to treat patients with brain tumors and cut aneous melanomas, epithermal neutron beams should be more useful becau se of their superior tissue-penetrating properties. Beam sources and c haracteristics will be discussed in the context of current and future BNCT trials. Finally, the past and present critical trials on BNCT for brain tumors will be reviewed and the future potential of BNCT will b e assessed.