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Sci Rep ; 8(1): 1141, 2018 01 18.
Article in English | MEDLINE | ID: mdl-29348437

ABSTRACT

Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy's ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.


Subject(s)
Boron Neutron Capture Therapy/methods , Boron/therapeutic use , Combined Modality Therapy/methods , Neutrons , Prostatic Neoplasms/radiotherapy , Proton Therapy , Proton Therapy/methods , Alpha Particles/therapeutic use , Animals , Borohydrides/chemistry , Boron/chemistry , Boron Neutron Capture Therapy/instrumentation , Carbon Isotopes/chemistry , Cell Death/radiation effects , Cell Line, Tumor , Chromosome Aberrations/radiation effects , Combined Modality Therapy/instrumentation , Cyclotrons , DNA Damage , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , DNA, Neoplasm/radiation effects , Dose-Response Relationship, Radiation , Fluorescent Dyes/chemistry , Humans , Karyotyping , Linear Energy Transfer , Male , Prostatic Neoplasms/pathology , Proton Therapy/instrumentation , Relative Biological Effectiveness , Sulfhydryl Compounds/chemistry
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