Experimental Set-up for FLASH Proton Irradiation of Small Animals Using a Clinical System

Purpose: Recent in vivo investigations have shown that short pulses of electrons at very high dose rates (FLASH) are less harmful to healthy tissues but just as efficient as conventional dose-rate radiation to inhibit tumor growth. In view of the potential clinical value of FLASH and the availability of modern proton therapy infrastructures to achieve this goal, we herein describe a series of technological developments required to investigate the biology of FLASH irradiation using a commercially available clinical proton therapy system. Methods and Materials: Numerical simulations and experimental dosimetric characterization of a modified clinical proton beamline, upstream from the isocenter, were performed with a Monte Carlo toolkit and different detectors. A single scattering system was optimized with a ridge filter and a high current monitoring system. In addition, a submillimetric set-up protocol based on image guidance using a digital camera and an animal positioning system was also developed. Results: The dosimetric properties of the resulting beam and monitoring system were characterized; linearity with dose rate and homogeneity for a 12 x 12 mm(2) field size were assessed. Dose rates exceeding 40 Gy/s at energies between 138 and 198 MeV were obtained, enabling uniform irradiation for radiobiology investigations of small animals in a modified clinical proton beam line. Conclusions: This approach will enable us to conduct FLASH proton therapy experiments on small animals, specifically for mouse lung irradiation. Dose rates exceeding 40 Gy/s were achieved, which was not possible with the conventional clinical mode of the existing beamline. (C) 2018 Elsevier Inc. All rights reserved.