The BELLA PW laser proton beamline: a new platform for ultra-high dose rate radiobiological research*

Radiotherapy is the current standard of care for more than 50% of all cancer patients. Improvements in radiotherapy technology have increased tumor targeting and normal tissue sparing. Recently, the beneficial differential effects on tumors versus normal tissues using the delivery of single, high radiation doses of >10 Gy at extremely high dose rates, has received increasing attention and was termed the FLASH effect. However, radiobiological research into radiobiological effectiveness of ultra-high dose rate protons has been limited by the restricted access to proton facilities for experiments. As such, there is much speculation regarding the underlying molecular and cellular mechanisms at play for irradiations with FLASH proton dose rates. We present the first radiobiological results using our new experimental platform to deliver petawatt laser-driven (LD) proton pulses with clinically relevant doses ranging from 5 to 25 Gy at ultra-high instantaneous dose rates of 10⁷ Gy/s with 2 MeV energy at 0.2 Hz repetition rate to prostate cell monolayers grown over a 1 cm diameter field. Dose-dependent cell survival measurements of human normal and tumor prostate cells exposed to either LD protons or conventional X-rays showed significantly higher normal cell survival after LD proton irradiation for total doses >10 Gy. The tumor cells in contrast showed enhanced killing after exposure. These results, in combination with the low-cost and small-footprint nature of LD proton sources, provide evidence to demonstrate the capabilities of this new platform to elucidate the mechanism and optimal conditions of ultra-high dose rate proton therapy.