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 α particles and recoil protons emitted by (10)B(n,α)(7)Li reaction. For BNCT to be effective, the tumor/normal tissue concentration ratio of (10)B must be larger than 1.0, because neutron distribution is not selective. We examined the combination of (10)B‐enriched borocaptate sodium (BSH) with flavone acetic acid (FAA) as a model compound which causes vascular collapse in squamous cell carcinoma in mice (SCCVII tumors) and would increase the tumor/normal tissue concentration ratio of (10)B. FAA (200 mg/kg, i.p.) was injected, and 5 min later BSH (75 mg/kg, i.v.) was administered, followed 15 to 180 min later by irradiation with thermal neutrons. The (10)B concentrations were measured by prompt gamma ray spectrometry. Without FAA, tumor (10)B concentrations were less than or equal to normal tissue concentrations at all time intervals, 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, (10)B concentrations 2.1‐ to 6.9‐fold greater in tumor than in muscle were achieved at all intervals tested. For blood and skin, significant differential accumulations were found in tumors at 120 and 180 min. Tumor/liver ratios were less than 1 at all times. Cell survival was determined by in vivo/in vitro colony assay, and increasing radiosensitization correlated with increasing tumor (10)B concentrations, whether or not they were achieved with FAA. Tumor control rates, determined at 180 days after BNCT, similarly appeared to depend only on (10)B levels at the time of irradiation. Because (10)B levels correlate with the radiation response of tissues, a therapeutic gain would be expected whenever the tumor levels exceed normal tissue levels, such as in tumors located in muscle irradiated at 15–180 min after FAA+BSH, or in those in skin irradiated at 120 and 180 min.