The Appropriate Conditions for the Cell Sparing (FLASH) Effect Exist in Ultra-high Dose Rate Carbon Ion Irradiation

Ultra-high dose rate irradiation (uHDR) (>40 Gy/s), commonly referred to as FLASH, has garnered attention in radiation therapy research due to its potential to mitigate damage to normal tissues while maintaining tumoricidal effects. Research on FLASH therapy using electron beams, X-rays, and proton beams has preceded studies using carbon ion beams. However, the clinical potential of FLASH carbon ion irradiation is increasingly being recognized, similar to other radiation modalities. This study aimed to evaluate the cell-sparing effect of carbon ion beams under normoxic conditions - a phenomenon that has not been previously reported.

Human salivary gland cell line (HSGc-c5), human dermal fibroblast (HDF) and human lung bronchial epithelial cell line (Nuli-1) were employed. In this study, we compared two types of linear energy transfer (19 and 50 keV/μm) and two oxygen concentrations (4% and 21%) to thoroughly investigate the cell-sparing effect, with cell death as the endpoint.

A significant cell-sparing effect was observed with carbon ion beam uHDR irradiation under normoxic conditions. Linear energy transfer (LET) influenced the manifestation of the sparing effect, with higher LET (50 keV/μm) demonstrating a stronger protective effect compared to lower LET (19 keV/μm). DNA damage, as indicated by γH2AX foci, was significantly reduced under uHDR compared to conventional dose rates.

Carbon ion uHDR irradiation induces a cell-sparing effect under normoxic conditions, which is influenced by LET and oxygen concentration. These findings provide essential insights into the mechanisms underlying the FLASH effect and pave the way for advancing the clinical application of uHDR carbon ion therapy.