FLASH vs. Conventional Dose Rate Proton Radiation in Mouse Abdomen

Abstract

<h3>Purpose/Objective(s)</h3> The mechanisms underlying normal tissue toxicity sparing and survival benefits of ultra-high dose rate radiation (FLASH) are still unclear. We used a low-energy proton system (50 MeV) optimized for small animal radiobiological research to study the biological effects after FLASH and conventional dose rate (CONV) proton radiation to mouse abdomen. <h3>Materials/Methods</h3> We radiated the abdomen of 6–7-week-old female C57BL/6 mice using the plateau region of a continuous (unpulsed) cyclotron-generated 50 MeV preclinical proton beam, transmitting through the abdomen, with 1.5cm (for survival study) or 3cm (for EdU assay) width of beam via customized vertical and horizontal collimators. Mice survival and regenerated crypts in colon tissues using EdU assay were studied. Mice were stratified into 3 groups: 1) control/sham radiation (n=8 for survival, n=4 for EdU); 2) FLASH (20Gy at 48-93Gy/sec, n=22 for survival and n=13 for EdU); 3) CONV (20Gy at ∼1Gy/sec, n=19 for survival, n=11 for EdU). For survival study, mice were observed for survival post radiation. For EdU assay, the mice were injected with EdU 3-4 hours prior to euthanasia, and colon tissues were collected at 24 hours and 96 hours post-radiation for sectioning and then EdU staining. <h3>Results</h3> FLASH and CONV groups showed different survival: FLASH (13 days post radiation, 36.4% survival); CONV (15.6% survival, P = 0.04). FLASH group had more EdU staining than the CONV group, though both FLASH and CONV groups showed reduced EdU staining compared to the control group. <h3>Conclusion</h3> Preliminary results of mouse abdomen FLASH and CONV proton radiation from a 50 MeV beam suggest FLASH proton radiation leads to better survival and less normal tissue damage than CONV radiation.