Abstract
Protontherapy (PT) is a fast-growing cancer therapy modality thanks to much-improved normal tissue sparing granted by the charged particles’ inverted dose-depth profile. Protons, however, exhibit a low biological effectiveness at clinically relevant energies. To enhance PT efficacy and counteract cancer radioresistance, Proton–Boron Capture Therapy (PBCT) was recently proposed. PBCT exploits the highly DNA-damaging α-particles generated by the p + 11B→3α (pB) nuclear reaction, whose cross-section peaks for proton energies of 675 keV. Although a significant enhancement of proton biological effectiveness by PBCT has been demonstrated for high-energy proton beams, validation of the PBCT rationale using monochromatic proton beams having energy close to the reaction cross-section maximum is still lacking. To this end, we implemented a novel setup for radiobiology experiments at a 3-MV tandem accelerator; using a scattering chamber equipped with an Au foil scatterer for beam diffusion on the biological sample, uniformity in energy and fluence with uncertainties of 2% and 5%, respectively, was achieved. Human cancer cells were irradiated at this beamline for the first time with 685-keV protons. The measured enhancement in cancer cell killing due to the 11B carrier BSH was the highest among those thus far observed, thereby corroborating the mechanistic bases of PBCT.
Highlights
The charged particle inverted dose-depth profile represents the physical pillar of protontherapy (PT), an advanced and rapidly spreading form of cancer radiotherapy (CRT) that makes use of high-energy accelerated proton beams to treat deep-seated tumours with elevated precision in dose deposition to the target volume [1,2]
We designed and implemented a radiobiology-dedicated beamline at the −40◦ beamline of the CIRCE accelerator. This allowed us to investigate in vitro the mechanistic basis of Proton–Boron Capture Therapy (PBCT) using low-energy monoenergetic proton beams
PBCT is an approach that had been hypothesized a few years ago to potentiate the limited usefulness of protontherapy (PT) towards radioresistant cancers based on the nuclear fusion reaction p + 11B→3α [11]
Summary
The charged particle inverted dose-depth profile represents the physical pillar of protontherapy (PT), an advanced and rapidly spreading form of cancer radiotherapy (CRT) that makes use of high-energy (typically up to 230 MeV) accelerated proton beams to treat deep-seated tumours with elevated precision in dose deposition to the target volume [1,2]. While unravelling existing uncertainties on proton radiobiology may lead to a re-assessment of both the clinical RBE used in PT, as well as of the cancer types eligible for PT [7,8], strategies aimed at potentiating proton biological efficacy are actively being sought [9,10] In this context, Yoon et al [11] proposed a novel binary approach termed Proton–Boron Capture Therapy (PBCT), based on the p + 11B→3α (pB) nuclear reaction, which presents a maximum of the cross-section for proton energy of 675 keV and can generate short-range α-particles that are densely ionizing, i.e., having a high Linear Energy Transfer (LET) [12]. This provides evidence in support of the biophysical rationale for PBCT-assisted enhancement of PT effectiveness
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