FLASH dose-rate helium ion beams: first in vitro investigations.

Abstract Purpose To establish and investigate the impact of dose, linear energy transfer (LET) and O2 concentration on biological response to ultra-high dose-rate (uHDR, FLASH) helium ion beams compared to standard dose-rate (SDR) irradiation. Methods and Materials Beam delivery settings for raster-scanned helium ions at both uHDR and SDR were tuned to achieve >100 Gy/s and ∼0.1 Gy/s, respectively. For both SDR and uHDR, plan optimization and calibration for 10 × 10mm2 fields was performed to assess in vitro response at LET range of 4.5-16 keV/µm. Clonogenic survival assay was conducted at doses ranging from 2 Gy to 12 Gy in two human lung epithelial cell lines (A549 and H1437). Radiation induced nuclear γH2AX foci (RIF) were assessed in both epithelial cell lines and primary human pulmonary fibroblasts. Results Average dose-rates achieved were 185 Gy/s and 0.12 Gy/s for uHDR and SDR, respectively. No differences in cellular response to SDR vs. uHDR were observed for all tested doses at 21% O2, as well as at 2 and 4 Gy at 1% O2. In contrast, at 1% O2 and dose threshold of ≳8Gy cell survival was higher and correlated with reduced nuclear γH2AX RIF signal indicating FLASH sparing effect in the investigated cell lines irradiated with uHDR as compared to SDR . Conclusion The first uHDR delivery of raster-scanned particle beams was achieved using helium ions, reaching FLASH-level dose-rates of >100 Gy/s.  Baseline oxygen levels and delivered dose (≳ 8 Gy) play a pivotal role, irrespective of the studied cell lines, for observation of a sparing effect for helium ions.