A New Low-Energy Proton Irradiation Facility to Unveil the Mechanistic Basis of the Proton-Boron Capture Therapy Approach

Featured Application The application of the work described herein is twofold: the possibility of routinely irradiating biological samples with high accuracy in energy and dose at a low-energy particle accelerator to gain insights into fundamental mechanisms of the biological action of charged particles; in a broader scenario, the possibility to potentiate the therapeutic capabilities of protontherapy through a method based on a nuclear physics reaction. 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 alpha-particles generated by the p + B-11 -> 3 alpha (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 B-11 carrier BSH was the highest among those thus far observed, thereby corroborating the mechanistic bases of PBCT.