Oxygen Depletion in Ultra-High Dose Rates for Protons And Electrons: Experimental Approach In Water And Biological Samples

Background and aims In FLASH radiotherapy (RT), a protective effect of healthy tissue was observed, while tumor control remains comparable to conventional RT[1]. One possible explanation is the oxygen depletion hypothesis, in which radiolysis of water/cytoplasma causes the production of radicals that then react with O2 dissolved in water. This would cause a reduction in O2, which results in a hypoxic target and thus a radio-protective effect. In a previous study[2], we measured O2 depletion in sealed water phantoms during irradiation at high dose rates (<300 Gy/s) for protons, carbon ions and photons. Methods In the study presented here, this experiment was conducted further to ultra-high dose rates (10^9 Gy/s) with protons at DRACO and electrons at ELBE, where also the impact of different pulse structures on O2 depletion was tested. In addition, various settings were tested in order to irradiate zebrafish embryos with FLASH while simultaneously measuring O2. Results and Conclusion We were able to confirm the results of the previous study even at ultra-high dose rates and with electrons and came to two conclusions: 1. not enough O2 was depleted at clinical doses to explain a FLASH effect based on radiation-induced hypoxia 2. the amount of O2 depleted per dose depends on dose rate, and higher dose rates deplete slightly less O2. Furthermore, it was possible to measure O2 depletion during zebrafish embryo irradiation making a simultaneous study of biological response and O2 depletion possible. [1]Favaudon, et al. (2014) https://doi.org/10.1126/scitranslmed.3008973 [2]Jansen, et al. (2021) https://doi.org/10.1002/mp.14917