FLASH Dose Rate Helium Ion Beams: First In Vitro Investigations

Abstract

To establish and investigate the effects of dose, linear energy transfer (LET), and O2 concentration on biologic response to ultrahigh dose rate (uHDR; FLASH) helium ion beams compared with standard dose rate (SDR) irradiation. 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 × 10-mm2 fields were performed to assess in vitro response at an LET range of 4.5 to 16 keV/µm. Clonogenic survival assay was conducted at doses ranging from 2 to 12 Gy in 2 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. 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 versus uHDR were observed for all tested doses at 21% O2, and at 2 and 4 Gy at 1% O2. In contrast, at 1% O2 and a dose threshold of ≳8 Gy cell survival was higher and correlated with reduced nuclear γH2AX RIF signal, indicating FLASH sparing effect in the investigated cell lines irradiated with uHDR compared with SDR. 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.