Ultrafast Tracking of Oxygen Dynamics During Proton FLASH

Area of Science:

• Radiation oncology
• Biophysics
• Biochemistry

Background:

• FLASH radiation therapy (RT) selectively protects normal tissues, offering a therapeutic advantage over conventional RT.
• The underlying mechanism of the FLASH effect is hypothesized to involve radiochemical oxygen depletion.
• Measuring oxygen dynamics during FLASH RT has been challenging due to the high dose rates.

Purpose of the Study:

• To develop and validate a method for measuring oxygen dynamics during FLASH RT.
• To investigate the role of oxygen depletion in the FLASH effect.
• To compare oxygen consumption between FLASH and conventional RT.

Main Methods:

• A novel phosphorescence quenching method was developed to track oxygen dynamics at rates up to ~3.3 kHz.
• Soluble Oxyphor probes were used for in vitro and in vivo measurements.
• Oxygen dynamics were assessed during proton FLASH irradiation.

Main Results:

• In vitro, oxygen depletion (g values) was higher for conventional irradiation than for FLASH RT.
• In low-oxygen conditions (<25 µM O2), oxygen depletion decreased with concentration for both methods.
• In vivo, a single FLASH irradiation was insufficient to cause severe hypoxia in well-oxygenated tissues.

Conclusions:

• The developed method enables real-time oxygen measurements during FLASH RT, crucial for radiobiological studies.
• The FLASH effect may be partly explained by differences in oxygen dependencies of oxygen consumption between conventional and FLASH RT.
• Further research into oxygen dynamics can help elucidate the FLASH effect mechanism.