Modification of the microstructure of the CERN- CLEAR-VHEE beam at the picosecond scale modifies ZFE morphogenesis but has no impact on hydrogen peroxide production.

FLASH has emerged as a significant breakthrough for the future of radiation oncology, as it reduces complications while preserving the tumor killing efficacy. To define the beam parameters for future clinical translation, Very High Energy Electrons (VHEE) delivered at CLEAR and able to reach deep seated tumors were used in conjunction with a FLASH-validated Intermediate Energy Electron (IIE) beam and a 160-225 keV X-ray beam, collectively able to deliver dose rates spanning from 1 Gy/min to 1011 Gy/s. High-throughput chemical assays were used to investigate radiochemical effects of FLASH, while zebrafish embryos served as a model to evaluate its impact on biological outcomes and morphogenesis. This study is the first comprehensive exploration investigating the impact of a large range of dose rates and various temporal parameters from early physico-chemical events to a complex biological system. Data derived at CLEAR revealed that the intensity of the bunch is a critical factor for observing the sparing effect of FLASH and uncovered an unforeseen biological response when electrons are delivered over the picosecond timescale. Present data also suggests that scanning with high intensity beamlets will be optimal for the future clinical translation of FLASH. HighlightsTo investigate the physics parameters required to trigger the FLASH sparing effect, CLEAR/VHEE/CERN beam macro/microstructure was varied. We show that delivery at the picosecond scale: - reduces alteration in the morphogenesis of zebrafish embryos, but - has no impact on secondary hydrogen peroxide production, Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=175 HEIGHT=200 SRC="FIGDIR/small/629203v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1df896aorg.highwire.dtl.DTLVardef@b6b824org.highwire.dtl.DTLVardef@1f35964org.highwire.dtl.DTLVardef@171d60f_HPS_FORMAT_FIGEXP M_FIG C_FIG