The radiation biology of boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a targeted radiation therapy that s ignificantly increases the therapeutic ratio relative to conventional radio therapeutic modalities. BNCT is a binary approach: A boron-10 (B-10)-labele d compound is administered that delivers high concentrations of B-10 to the target tumor relative to surrounding normal tissues. This is followed by i rradiation with thermal neutrons or epithermal neutrons which become therma lized at depth in tissues. The short range (5-9 mu m) of the alpha and Li-7 particles released from the B-10(n,alpha)Li-7 neutron capture reaction mak e the microdistribution of B-10 of critical importance in therapy. The radi ation field in tissues during BNCT consists of a mixture of components with differing LET characteristics. Studies have been carried out in both norma l and neoplastic tissues to characterize the relative biological effectiven ess of each radiation component. The distribution patterns and radiobiologi cal characteristics of the two B-10 delivery agents in current clinical use , the amino acid p-boronophenylalanine (BPA) and the sulfhydryl borane (BSI ), have been evaluated in a range of normal tissues and tumor types. Consid ered overall, BSH-mediated BNCT elicits proportionately less damage to norm al tissue than does BNCT mediated with BPA. However, BPA exhibits superior in vivo tumor targeting and has proven much more effective in the treatment of brain tumors in rats. In terms of fractionation effects, boron neutron capture irradiation modalities are comparable with other high-LET radiation modalities such as fast-neutron therapy. There was no appreciable advantag e in increasing the number of daily fractions of thermal neutrons beyond tw o with regard to sparing of normal tissue in the rat spinal cord model. The experimental studies described in this review constitute the radiobiologic al basis for the new BNCT clinical trials for glioblastoma at Brookhaven Na tional Laboratory, at the Massachusetts Institute of Technology, and at the High Flux Reactor, Petten, The Netherlands. The radiobiology of experiment al and clinical BNCT is discussed in detail. (C) 1999 by Radiotion Research Society.