Feasibility of proton FLASH effect tested by zebrafish embryo irradiation

Background and purpose Motivated by first animal trials showing the normal tissue protecting effect of electron and photon Flash irradiation relative to conventional continuous beam delivery, the feasibility of proton Flash should be assessed. Materials and methods A setup and beam parameter settings for the treatment of zebrafish embryo with proton Flash and proton beam of conventional dose rate were established at the University Proton Therapy Dresden. Zebrafish embryos were treated with graded doses and the differential effect on embryonic survival and the induction of morphological malformations was followed for up to four days after irradiation. Results Beam parameters for the realization of proton Flash were set and tested with respect to controlled dose delivery to biological samples. The dose dependent embryonic survival data obtained for protons delivered as Flash and with a beam of conventional dose rate of 5 Gy/min show not significant influence of proton dose rate. Similarly, just a trend towards a protective effect of proton Flash was revealed for the induction of pericardial oedema as one type of acute radiation effect and spinal curvature as a developmental abnormality. Conclusion The feasibility of Flash proton irradiation was successfully shown, whereas more experiments are required to understand the absence of a clear protecting effect and therefore to figure out the limits and requirements for the Flash effect.