EFFECTS OF BORON NEUTRON-CAPTURE THERAPY USING BOROCAPTATE SODIUM IN COMBINATION WITH A TUMOR-SELECTIVE VASOACTIVE AGENT IN MICE

Boron neutron capture therapy (BNCT) destroys tumor cells by means of alpha particles and recoil protons emitted by B-10(n,alpha)Li-7 reacti on, For BNCT to he effective, the tumor/normal tissue concentration ra tio of B-10 must he larger than 1.0, because neutron distribution is n ot selective, We examined the combination of B-10-enriched borocaptate sodium (BSH) with flavone acetic acid (FAA) as a model compound which causes vascular collapse in squamous cell carcinoma in mice (SCCVII t umors) and would increase the tumor/normal tissue concentration ratio of B-10. FAA (200 mg/kg, i.p.) was injected, and 5 min later BSH (75 m g/kg, i.v.) was administered, followed 15 to 180 min later by irradiat ion with thermal neutrons, The B-10 concentrations were measured by pr ompt gamma ray spectrometry Without FAA, tumor B-10 concentrations wer e less than or equal to normal tissue concentrations at all time inter vals, except that the concentrations were 1.7- to 2.7-fold greater in tumor than muscle at 15 and 180 min after injection of BSH. With FAA, B-10 concentrations 2.1- to 6.9-fold greater in tumor than in muscle w ere achieved at all intervals tested, For blood and skin, significant differential accumulations were found in tumors at 120 and 180 min, Tu mor/liver ratios were less than 1 at all times, Cell survival was dete rmined by in vivo/in vitro colony assay, and increasing radiosensitiza tion correlated with increasing tumor B-10 concentrations, whether or not they were achieved with FAA. Tumor control rates, determined at 18 0 days after BNCT, similarly appeared to depend only on B-10 levels at the time of irradiation, Because B-10 levels correlate with the radia tion response of tissues, a therapeutic gain would he expected wheneve r the tumor levels exceed normal tissue levels, such as in tumors loca ted in muscle irradiated at 15-180 min after FAA+BSH, or in those in s kin irradiated at 120 and 180 min.