Boron neutron capture therapy (BNCT) destroys
tumor cells by means of alpha particles and recoil
protons emitted by 10B(n, alpha)7Li reaction. For BNCT to be effective, the
tumor/normal tissue concentration ratio of 10B must be larger than 1.0, because neutron distribution is not selective. We examined the combination of 10B-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 10B. 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 10B concentrations were measured by prompt gamma ray spectrometry. Without FAA,
tumor 10B 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, 10B 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 10B concentrations, whether or not they were achieved with FAA.
Tumor control rates, determined at 180 days after BNCT, similarly appeared to depend only on 10B levels at the time of irradiation. Because 10B 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.