FLASH Dose-Rate Helium Ion Beams: First In Vitro Investigations

Abstract

<h3>Purpose/Objective(s)</h3> To establish and investigate the impact of LET and O₂ concentration on biological response to ultra-high dose-rate (uHDR, FLASH) helium ion beams compared to standard dose-rate (SDR) irradiation. <h3>Materials/Methods</h3> Beam delivery settings for raster-scanned helium ions at both uHDR and SDR were tuned to achieve > 100 Gy/s and 0.15 Gy/s, respectively. For both SDR and uHDR, 8 Gy and 12 Gy plan optimization and calibration for 10 × 10mm² fields was performed to assess <b>in vitro</b> response at lower LET (4.5 keV/μm) and higher LET (16 keV/μm) conditions. Clonogenic assay and DNA damage response (γH2AX) of human lung epithelial cancer cells A549 cells were used as biological indicators for the cellular response to uHDR and SDR irradiation for specified oxygen concentrations levels (1%, 21%). <h3>Results</h3> Average dose-rates for both lower and higher LET were 193 Gy/s and 0.15 Gy/s for uHDR and SDR, respectively. Cell survival was higher and γH2AX, a surrogate for DNA damage response, was lower for cells irradiated with uHDR as compared to SDR at 1% O₂ for both dose and LET levels. This difference in cellular response was not seen at 21% O₂ where cell survival and DNA damage response were unchanged at studied dose-rates. <h3>Conclusion</h3> 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 play a pivotal role, irrespective of investigated LET, for observation of a sparing effect for helium ions.