Beam pulse structure and dose rate as determinants for the flash effect observed in zebrafish embryo

Background and purpose: Continuing recent experiments at the research electron accelerator ELBE at the Helmholtz-Zentrum Dresden-Rossendorf the influence of beam pulse structure on the Flash effect was investigated. Materials and methods: The proton beam pulse structure of an isochronous cyclotron (UHDRiso) and a syn-chrocyclotron (UHDRsynchro) was mimicked at ELBE by quasi-continuous electron bunches at 13 MHz delivering mean dose rates of 287 Gy/s and 177 Gy/s and bunch dose rates of 106 Gy/s and 109 Gy/s, respectively. For UHDRsynchro, 40 ms macro pulses at a frequency of 25 Hz superimposed the bunch deliv-ery. For comparison, a maximum beam intensity (2.5 x 105 Gy/s mean and-109 Gy/s bunch dose rate) and a reference irradiation (of-8 Gy/min mean dose rate) were applied. Radiation induced changes were assessed in zebrafish embryos over four days post irradiation. Results: Relative to the reference a significant protecting Flash effect was observed for all electron beam pulse regimes with less severe damage the higher the mean dose rate of the electron beam. Accordingly, the macro pulsing induced prolongation of treatment time at UHDRsynchro regime reduces the protecting effect compared to the maximum regime delivered at same bunch but higher mean dose rate. The Flash effect of the UHDRiso regime was confirmed at a clinical isochronous cyclotron comparing the damage induced by proton beams delivered at 300 Gy/s and-9 Gy/min. Conclusion: The recent findings indicate that the mean dose rate or treatment time are decisive for the normal tissue protecting Flash effect in zebrafish embryo.