Investigating the oxygen dependence of FLASH-RT using electron paramagnetic resonance imaging

Area of Science:

• Radiation oncology
• Radiobiology
• Medical physics

Background:

• The FLASH effect, a phenomenon where ultra-high dose rate radiation spares healthy tissue, is not fully understood.
• Limited data suggests oxygen plays a role in the FLASH effect, but its precise impact remains unclear.

Purpose of the Study:

• To investigate the influence of tissue oxygen tension (pO2) on gastrointestinal (GI) sparing in mice undergoing FLASH radiation therapy.
• To compare GI toxicity and sparing between male and female mice under varying oxygen conditions.

Main Methods:

• Tissue pO2 was measured noninvasively using electron paramagnetic resonance imaging (EPRI) and a phosphorescent microsensor in mice breathing different oxygen concentrations (10%, 21%, 95%).
• Mice underwent total abdominal irradiation using either FLASH or conventional (CONV) dose rates.
• Gastrointestinal toxicity was assessed using the regenerating crypt assay.

Main Results:

• In vivo pO2 positively correlated with breathing-gas oxygen concentration across multiple organs.
• Male mice exhibited lower pO2 compared to female mice under certain oxygen conditions.
• Both FLASH and CONV irradiation showed decreased GI toxicity with lower pO2. Male mice demonstrated significant FLASH GI sparing, outperforming female mice across conditions.

Conclusions:

• GI toxicity from both CONV and FLASH irradiation is significantly correlated with in vivo oxygen tension.
• Age-matched male and female mice display differential radiosensitivity to FLASH irradiation, influenced by breathing-gas conditions.