Mean dose rate in ultra-high dose rate electron irradiation is a significant predictor for O₂ consumption and H₂O₂ yield

Abstract

Objective: The objective of this study was to investigate the impact of mean and instantaneous dose rates on the production of reactive oxygen species (ROS) during ultra-high dose rate (UHDR) radiotherapy. The study aimed to determine whether either dose rate type plays a role in driving the FLASH effect, a phenomenon where UHDR radiotherapy reduces damage to normal tissues while maintaining tumor control.
Approach: Assays of hydrogen peroxide (H2O2) production and oxygen consumption (ΔpO2) were conducted using UHDR electron irradiation. Aqueous solutions of 4% albumin were utilized as the experimental medium. The study compared the effects of varying mean dose rates and instantaneous dose rates on ROS yields. Instantaneous dose rate was varied by changing the source-to-surface distance (SSD), resulting in instantaneous dose rates ranging from 102 to 106 Gy/s. Mean dose rate was manipulated by altering the pulse frequency of the linear accelerator (linac) and by changing the SSD, ranging from 0.14 to 1500 Gy/s. 
Main Results: The study found that both ΔH2O2 and ΔpO2 decreased as the mean dose rate increased. Multivariate analysis indicated that instantaneous dose rates also contributed to this effect. The variation in ΔpO2 was dependent on the initial oxygen concentration in the solution. The molar yield was estimated to be 7.51 mol H2O2 per mol O2 based on the analysis of dose rate variation.
Significance: The results highlight the significance of mean dose rate as a predictor of ROS production during UHDR radiotherapy. As the mean dose rate increased, there was a decrease in oxygen consumption and in H2O2 production. These findings have implications for understanding the FLASH effect and its potential optimization. The study sheds light on the role of dose rate parameters and their impact on radiochemical outcomes, contributing to the advancement of UHDR radiotherapy techniques.

FLASH Radiotherapy: Expectations, Challenges, and Current Knowledge

“…Among these parameters, the beam temporal structure was varied to investigate oxygen depletion in water [ 77 ], measuring O 2 content for different average and bunch dose rates of electron beams, showing a strong correlation with biological data, and supporting the role of radicals at the origin of the FLASH effect. In another study [ 78 ], the dependence of O 2 consumption and H 2 O 2 production were found to depend on the mean dose rate, with instantaneous dose rates also contributing to this effect. Concerning the type of radiation, interesting studies are finally emerging on the use of UHDR kilovoltage (kV) X-rays from a rotating-anode X-ray source for in vivo studies, making this type of radiation easily accessible at a laboratory scale compared to synchrotron radiation [ 79 ].…”