Proton Irradiations at Ultra-High Dose Rate vs. Conventional Dose Rate: Strong Impact on Hydrogen Peroxide Yield

Abstract

During ultra-high dose rate (UHDR) external radiation therapy, healthy tissues appear to be spared while tumor control remains the same compared to conventional dose rate. However, the understanding of radiochemical and biological mechanisms involved are still to be discussed. This study shows how the hydrogen peroxide (H2O2) production, one of the reactive oxygen species (ROS), could be controlled by early heterogenous radiolysis processes in water during UHDR proton-beam irradiations. Pure water was irradiated in the plateau region (track-segment) with 68 MeV protons under conventional (0.2 Gy/s) and several UHDR conditions (40 Gy/s to 60 kGy/s) at the ARRONAX cyclotron. Production of H2O2 was then monitored using the Ghormley triiodide method. New values of GTS(H2O2) were added in conventional dose rate. A substantial decrease in H2O2 production was observed from 0.2 to 1.5 kGy/s with a more dramatic decrease below 100 Gy/s. At higher dose rate, up to 60 kGy/s, the H2O2 production stayed stable with a mean decrease of 38% ± 4%. This finding, associated to the decrease in the production of hydroxyl radical (•OH) already observed in other studies in similar conditions can be explained by the well-known spur theory in radiation chemistry. Thus, a two-step FLASH-RT mechanism can be envisioned: an early step at the microsecond scale mainly controlled by heterogenous radiolysis, and a second, slower, dominated by O2 depletion and biochemical processes. To validate this hypothesis, more measurements of radiolytic species will soon be performed, including radicals and associated lifetimes.

A method to implement inter-track interactions in Monte Carlo simulations with TOPAS-nBio and their influence on simulated radical yields following water radiolysis

“…While the results of the simulation studies show a similar trend of the G-values with an increasing number of inter-track interaction or the dose rate, experimental results are not straightforward. On the one hand, Kusumoto et al (2020) observed a decrease of • OH with increasing dose rate, as investigated in the simulation studies, but on the other hand, a decrease of H 2 O 2 with increasing dose rate was observed in some experimental trials (Montay-Gruel et al 2019, Blain et al 2022). This is in direct conflict with the results of our study and the mentioned simulation studies.…”

Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation

“…The importance of the chemical processes, such as oxygen depletion and radical-radical interaction, during/ after UHDR irradiation for the sparing effect has long been discussed (Kirby-Smith and Dolphin 1958, Dewey and Boag 1959, Berry et al 1969, Berry and Stedeford 1972, Ling et al 1978, Spitz et al 2019, Vozenin et al 2019, Favaudon et al 2021. Recent studies, for instance, estimated reductions in the yield of hydrogen peroxide (Montay-Gruel et al 2019, Blain et al 2022, Kacem et al 2022 and hydroxyl radical (•OH) that is one of types of reactive species (Kusumoto et al 2020(Kusumoto et al , 2022 with dose rate escalation, suggesting that the decrement of reactive species might be due to the oxygen depletion or the radical-radical reactions. As a result of decreased deleterious •OH at UHDR, DNA damage induction, an early biological effect of radiation exposure, has been believed to be reduced compared to the CONV dose rate (Ohsawa et al 2022, Konishi et al 2023, and such depression of DNA damage might result in expression of the sparing effect after FLASH-RT.…”

Behavior of Portlandite upon Exposure to Ionizing Radiation: Evidence of Delayed H2 Production

“…Even if γ rays and accelerated electrons have the same linear energy transfer value, γ-rays provide a relatively low dose rate (continuous beam), whereas electron pulses deliver an ultrahigh dose rate irradiation into the material (pulsed beam). A change of several orders of magnitude in the dose rate is well-known to affect the amount of produced species. − It is therefore interesting to evaluate this discrepancy in H 2 production in irradiated portlandite. The shape of the H 2 production measured is very similar no matter the dose rate (see Figures and for the purpose of comparison).…”