Proton Irradiation Platforms for Preclinical Studies of High-Dose-Rate (FLASH) Effects at RARAF.

Area of Science:

• Medical Physics
• Radiation Oncology
• Preclinical Research

Background:

• Proton FLASH therapy offers potential advantages but faces challenges due to limited availability of specialized high-dose-rate irradiators.
• Preclinical research is crucial for understanding proton FLASH therapy's biological effects and optimizing treatment parameters.

Purpose of the Study:

• To develop and validate accessible proton irradiation platforms for high-dose-rate (≥100 Gy/s) preclinical studies.
• To investigate the impact of varying proton dose rates on cancer cell survival and oxygen depletion in aqueous solutions.

Main Methods:

• Assembly and optimization of two distinct proton irradiation platforms with custom sample holders.
• Development and testing of dosimetry protocols for accurate dose delivery at high instantaneous dose rates.
• Fabrication of a microfluidic device for irradiating biological samples in suspension.
• Experimental validation using cancer cell lines and Fricke solution to assess dose-rate effects.

Main Results:

• No significant dose-rate-dependent variation in cancer cell survival was observed up to 10 Gy across dose rates of 0.1, 10, and 100 Gy/s.
• Irradiation of Fricke solution at 1,000 Gy/s demonstrated complete oxygen depletion at 107 Gy (21% oxygen) and 56 Gy (4% oxygen).

Conclusions:

• The developed proton irradiation platforms are versatile and suitable for diverse preclinical research applications in radiation oncology.
• Findings suggest that proton dose rate may not significantly impact cancer cell survival at clinically relevant doses, warranting further investigation.
• The platforms facilitate crucial studies on water radiolysis and oxygen depletion dynamics under ultra-high dose rate conditions.