title: L-Phenylalanine preloading reduces the (10)B(n, α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.
abstract: Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours.
authors.affiliation: Particle Radiation Oncology Research Center, Kyoto University Research Reactor Institute, Osaka 590-0494, Japan; Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Particle Radiation Oncology Research Center, Kyoto University Research Reactor Institute, Osaka 590-0494, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Nuclear Science and Engineering, Kyoto University Research Reactor Institute, Osaka 590-0494, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukutani
authors.affiliation: Particle Radiation Oncology Research Center, Kyoto University Research Reactor Institute, Osaka 590-0494, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.affiliation: Department of Nuclear Science and Engineering, Kyoto University Research Reactor Institute, Osaka 590-0494, Japan. Electronic address: onokoji@rri.kyoto-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
mesh_terms: D001896:Boron Compounds / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010649:Phenylalanine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D011829:Radiation Dosage
chemical_list: C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D010649:Phenylalanine
keywords: Boron neutron capture therapy; Brain necrosis; Brain tumour; Compound biological effectiveness factor; L-BPA