Open AccessEffects of Boron Neutron Capture Therapy Using Borocaptate Sodium in Combination with a Tumor‐selective Vasoactive Agent in Mice
Author(s) -
Ono Koji,
Masunaga Shinichiro,
Kinashi Yuko,
Takagaki Masao,
Akaboshi Mitsuhiko,
Suzuki Minoru,
Baba Hideo
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00567.x
Subject(s) - in vivo , chemistry , radiochemistry , in vitro , neutron capture , irradiation , boron , biology , biochemistry , microbiology and biotechnology , organic chemistry , physics , nuclear physics
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.