Laser-induced FLASH very-high-energy electron irradiation for cancer research

The FLASH effect induced by ultrahigh dose rates ionizing radiation has been shown to maintain anti-tumor efficacy in animal models, while sparring the functionality of normal tissue. We evaluate herein this effect for very high-energy electron (VHEEs) irradiation with a goal for better understanding of the FLASH effect at cellular and molecular level. High-intensity petawatt laser-driven accelerators were employed to deliver FLASH-VHEEs at ultrahigh dose rates in very short pulses. Melanoma cancer cells and normal melanocyte cocultures were simultaneously exposed to VHEEs. The largest fraction of DNA-containing nuclei damaged by the electron was reached in discrete irradiated areas of the cell monolayers at a cumulative dose one order of magnitude lower than that obtained by pulsed X-ray irradiation. We also observed that normal cells were less affected than cancer cells after electron exposure. We further propose tumor-on-a-chip models to explore mechanisms behind cellular response to unconventional irradiation radiotherapy schemes.