Mean dose rate in ultra-high dose rate electron irradiation is a significant predictor for O 2 consumption and H 2 O 2 yield.
Jacob P SunnerbergRongxiao ZhangDavid GladstoneHarold M SwartzJiang GuiBrian W PoguePublished in: Physics in medicine and biology (2023)
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 (H 2 O 2 ) production and oxygen consumption (ΔpO 2 ) 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 10 2 to 10 6 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 ΔH 2 O 2 and ΔpO 2 decreased as the mean dose rate increased. Multivariate analysis indicated that instantaneous dose rates also contributed to this effect. The variation in ΔpO 2 was dependent on the initial oxygen concentration in the solution. The molar yield was estimated to be 7.51 mol H 2 O 2 per mol O 2 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 H 2 O 2 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.
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