Boron Neutron Capture Therapy of Cancer

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Boron neutron capture therapy is based on the nuclear reac tion that occurs ..... ports of all of these reactors have a geometry that reduces fast neutron and 7-.
Boron Neutron Capture Therapy of Cancer Rolf F. Barth, Albert H. Soloway and Ralph G. Fairchild Cancer Res 1990;50:1061-1070.

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[CANCER RESEARCH 50. 1061-1070. February 15. 1990)

Perspectives in Cancer Research

Boron Neutron Capture Therapy of Cancer1 Rolf F. Barth,2 Albert H. Soloway, and Ralph G. Fairchild Department of Pathology and College of Pharmacy, The Ohio State L'nirersily. Columbus, Ohio 43210 ¡R.F. B., A. H. S./, and Medical Department, Brookhaven National Laboratory, L'pton. Long Island, New York 11973 [R. G. F.J

nuclides that have high neutron capture cross-sections, "'B is the most attractive for the following reasons: (a) it is nonradioactive and readily available, comprising approximately 20% of naturally occurring boron; (b) the particles emitted by the capture reaction [l('B(n,«)7Li]are largely high LET; (c) their path lengths are approximately 1 cell diameter (10-14 /jm), theoretically limiting the radiation effect to those tumor cells that have taken up a sufficient amount of IOBand simultane

Boron neutron capture therapy is based on the nuclear reac tion that occurs when a stable isotope, '"B, is irradiated with low energy (0.025 eV) or thermal neutrons to yield stripped down helium nuclei («-particles) and 7Li nuclei. /He + 7Li + 2.79 MeV (6%) —¿ Õ

4He + 7Li + 0.48 MeV 7 + 2.31 MeV (94%)

The therapeutic potential of this reaction was recognized by Locher over 50 years ago (1), but it was Sweet (2-4), who first suggested that BNCT1 might be useful for the treatment of brain tumors. Shortly thereafter, a clinical trial was initiated at the Brookhaven National Laboratory in cooperation with Sweet and others at the Massachusetts General Hospital utilizing borax as the capture agent (5, 6). The objective at that time was to use BNCT as an adjunct to surgery for the treatment of patients with the most highly malignant and therapeutically refractory of all brain tumors, glioblastoma multiforme. Further trials were carried out in the early 1960s, but as will be described in more detail later on, these failed to show any evidence of therapeutic efficacy (5-7) and were associated with adverse effects in normal tissues (7). Stimulated by the more encour aging clinical studies of Hatanaka et al. (8, 9) for the treatment of malignant gliomas and those of Mishima et al. (10) for melanoma, there has been renewed national and international interest in BNCT. The theoretical advantage of BNCT is that it is a two component or binary system, consisting of 10Band thermal neutrons, which when combined together generate high LET radiation capable of selectively destroying tumor cells without significant damage to normal tissues. In order for BNCT to succeed a critical amount of 10B and a sufficient number of thermal neutrons must be delivered to individual tumor cells. Over the past few years the Department of Energy and the NIH have renewed funding for BNCT-related research, and this has supported a growing number of investigators in many different disciplines. Advances in BNCT in the areas of compound distribution and pharmacokinetics compare favora bly with other emerging modalities such as photon activation therapy, photodynamic therapy, and the use of radiolabeled antibodies for cancer treatment in which physiological targeting is used. There are a number of nuclides that have a high propensity for absorbing low energy or thermal neutrons (Table 1), and this property, referred to as the neutron capture cross-section (