Purpose: To determine the biological effects of FLASH proton radiotherapy (F-PRT) using the spread out Bragg peak (SOBP) compared to standard dose rate proton radiotherapy (S-PRT) in a whole abdomen mouse model.
Methods: An IBA Proteus Plus C230 Cyclotron was used to deliver 230 MeV proton beams (range 32 g/cm2) to a fixed beam line in a dedicated research room. An SOBP was generated with a custom made ridge filter placed between the first and second scatterer in the beam. Range shifting material was placed prior to the final collimator to irradiate mouse whole abdomen with the SOBP. To investigate the acute radiation damage, 8-10 week old C57BL/6J mice were randomly assigned to 15 Gy whole abdomen irradiation into one of four groups: (1) SOBP F-PRT, (2) SOBP S-PRT, (3) entrance F-PRT, (4) entrance S-PRT. Mice were injected with EdU at 3.5 days after irradiation and jejunum segments were harvested and preserved for further staining. Upon staining, EdU-positive proliferating cells and regenerated intestinal crypts were quantified.
Results: The generated SOBP had a modulation (width) of 2.5 cm from the proximal to distal 90%. Mice were irradiated with FLASH dose rates of 101.3±2.8 Gy/s and standard dose rates of 0.94±0.02 Gy/s with a SOBP. Using the entrance region of the proton beam, dose rates were 115.4±7.4 Gy/s and 1.1±0.01 Gy/s for F-PRT and S-PRT, respectively. Film irradiation showed uniform dose delivery across the whole abdomen throughout the mouse body width. FLASH preserved a significantly higher percentage of regenerated crypts compared to standard dose rate radiation using both the entrance and SOBP.
Conclusion: SOBP F-PRT beams were delivered to healthy mouse whole abdomen. FLASH-irradiated mice exhibited normal tissue sparing when compared to S-PRT. SOBP for proton FLASH can lead to better dose conformality around targets and increased normal tissue sparing.