Proton Irradiation Platforms for Preclinical Studies of High-Dose-Rate (FLASH) Effects at RARAF

Limited availability of proton irradiators optimized for high-dose-rate studies makes the preclinical research of proton FLASH therapy challenging. We assembled two proton irradiation platforms that are capable of delivering therapeutic doses to thin biological samples at dose rates equal to and above 100 Gy/s. We optimized and tested dosimetry protocols to assure accurate dose delivery regardless of the instantaneous dose rate. The simplicity of the experimental setups and availability of custom-designed sample holders allows these irradiation platforms to be easily adjusted to accommodate different types of samples, including cell monolayers, 3D tissue models and small animals. We have also fabricated a microfluidic flow-through device for irradiations of biological samples in suspension. We present one example of a measurement with accompanying preliminary results for each of the irradiation platforms. One irradiator was used to study the role of proton dose rate on cell survival for three cancer cell lines, while the other was used to investigate the depletion of oxygen from an aqueous solution by water radiolysis using short intense proton pulses. No dose-rate-dependent variation was observed between the survival fractions of cancer cells irradiated at dose rates of 0.1, 10 and 100 Gy/s up to 10 Gy. On the other hand, irradiations of Fricke solution at 1,000 Gy/s indicated full depletion of oxygen after proton doses of 107 Gy and 56 Gy for samples equilibrated with 21% and 4% oxygen, respectively.