Partial abdominal carbon-ion FLASH irradiation spares lethality compared to conventional irradiation: impact of LET and dose rate

Ultra-high dose rate (FLASH) therapy has attracted attention for its potential to effectively target tumors while preserving healthy tissues. Although the biological effects of FLASH therapy have been well-documented with electrons, photons, and protons, data regarding carbon-ions are limited. This study aimed to investigate the biological effects of carbon-ions on the intestines of mice to determine whether carbon-ions exhibit the FLASH effect. Simultaneously, we aimed to identify the parameters influencing its occurrence. Partial abdominal irradiation was performed on C3H/He mice using 290 MeV/u FLASH and conventional dose rate (CONV) carbon-ions under both low and high linear energy transfer (LET). The evaluation included the 30-day survival rate, body weight changes, and stool pellet alterations within 14 days after irradiation. Furthermore, we assessed the number of regenerating crypts 3.5 days after irradiation. Under low-LET, FLASH and CONV irradiation exhibited comparable sparing effects on normal intestinal tissues. However, FLASH significantly improved the survival rate of mice under high-LET, when the dose rate exceeded 100 Gy/s. The number of regenerating crypts 3.5 days after irradiation was 1.5 times higher in the FLASH group than in the CONV group. The results indicate that carbon-ion FLASH exhibits the FLASH effect at high-LET with dose rate and LET identified as critical parameters influencing the FLASH effect.