Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends Upon Baseline Tissue Oxygenation.

PURPOSE

This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.

METHODS AND MATERIALS

Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator. Oxyphor PdG4 was administered into the subcutaneous tissue of the flank skin 1 hour before irradiation. Skin oxygen tension (pO) was manipulated by adjusting oxygen content in the inhaled gas mixture and/or by vasculature compression. A skin surface radiation dose of 19.8 ± 0.3 Gy was verified using a calibrated semiconductor diode dosimeter. Dose rate was varied across the UHDR range by changing linear accelerator cone length and pulse repetition frequency.

RESULTS

The decrease in pO per unit dose during radiation delivery, termed oxygen consumption g-value (g, mmHg/Gy), was significantly influenced by tissue oxygen levels in the range 0 to 65 mmHg under UHDR conditions. Within the 0 to 20 mmHg range, g exhibited a sharp increase with rising baseline pO, plateauing at 0.26 mmHg/Gy. Dose rate variations (mean values, 25-1170 Gy/s; per pulse doses of 2.5-9.8 Gy) were explored by varying both cone length and pulse repetition frequency (10-120 Hz) with no significant changes in g. Conventional dose rate irradiation resulted in no discernible changes in pO.

CONCLUSIONS

The results show significant differences in the radiation-chemical effects of UHDR radiation between hypoxic and well-oxygenated tissues. Similar trends between earlier published in vitro and in vivo experiments presented herein suggest the chemical mechanisms driving the dependencies of g on pO are similar, potentially underpinning the FLASH effect. Importantly, significant variations in baseline pO were observed in animals kept under identical conditions, underscoring the necessity to control and monitor tissue oxygen levels for preclinical investigations and future clinical applications of FLASH radiation therapy.