RT-6 POTENTIAL AND PROSPECTS OF BORON NEUTRON CAPTURE THERAPY USING A COMBINATION OF MULTIPLE BORON AGENTS

Abstract

Abstract Boron neutron capture therapy (BNCT) is a particle therapy that can target tumors at the cellular level. BNCT has been developed for the treatment of malignant gliomas with widely infiltrated tumors, but as the indication for BNCT was expanded to include the whole body, the focus shifted to borophalan-10B (BPA), which is based on the essential amino acid phenylalanine, as a candidate agent. We started BNCT for brain tumors in 2002 with a protocol combining two compounds (BPA, BSH) that had been clinically used, but later, with the development of an accelerator-based system, we conducted a clinical study of a single agent of BPA with a modified administration protocol in a nuclear reactor. In this report, we analyze the clinical studies of BNCT for recurrent malignant glioma using the reactor as a neutron source, and discuss the possibility of BNCT using multiple drugs in combination. The median survival with BSH+BPA was 11.0 months (n=29) overall, and the MST with BPA alone was 11.1 months (n=24), with similar results for BPA alone. The blood boron levels at the time of irradiation were 46.3 and 27.3 μg/ml, respectively, which were higher with the addition of BSH. The irradiation doses converted to X-rays (Gy) equivalent were calculated to be 69 and 76 Gy-Eq for the maximum tumor, 37 and 40 Gy-Eq for the minimum, and 10.9 and 10.5 Gy-Eq for the normal brain, respectively. The biological effectiveness ratios for tumor and normal tissue from neutron capture reactions with boron compounds and tissue boron concentrations were factored into these calculations, and since BPA and BSH have different target systems (BPA in the infiltration zone and BSH in the contrast zone, respectively), we believe that their combined use may improve therapeutic efficacy and attenuate adverse events.