Multiscale Radiobiological Assessment of Laser-Driven Very High Energy Electrons Versus Conventional Electrons

This study systematically investigates the radiobiological effects of very high energy electrons (VHEE) generated by a laser-plasma accelerator (LPA), in comparison with conventional intermediate energy electrons (CIEE) from a conventional linear accelerator. Using in vitro, ex vivo, and in vivo models, we evaluate and compare their potential toxicity on healthy tissues.

Cell viability, tissue response, and developmental toxicity were assessed across 3 biological models. In vitro, hTERT-immortalized, human fibroblasts (MRC5-hTERT) were used to generate postirradiation viability-based survival curves following a dose escalation of 2 to 10 Gy. Ex vivo, mouse precision-cut lung slices were analyzed for radiation-induced inhibition of cell replication after 3, 6, and 9 Gy. In vivo, zebrafish embryos were irradiated with 6 and 9 Gy and subsequently evaluated for developmental toxicity through body length and spinal curvature measurements. VHEE irradiations were delivered using the Salle Jaune LPA (Laboratoire d'Optique Appliquée), generating a broad-spectrum electron beam with a mean energy of 140.6 MeV at the biological target, while CIEE irradiations were performed using a conventional 7 MeV linear accelerator (Institut Curie).

In vitro, MRC5-hTERT cells showed no significant difference in radiosensitivity between VHEE and CIEE conditions, with comparable $D_{10}$ values (P value $=.7$ ). In the ex vivo model, both beams induced a dose-dependent decrease in cell division with no significant interbeam differences at any dose level (P value $>.99$ ). In vivo, zebrafish embryos exhibited dose-dependent body shortening and increased spinal curvature following both VHEE and CIEE exposure. No significant differences were observed between the 2 modalities at matched doses for any measured metric (P value $\ge .5$ ).

To our knowledge, this study presents the first multiscale radiobiological evaluation of a laser-driven VHEE beam across cellular, tissue, and organismal levels. Under the investigated conditions, VHEE and CIEE irradiations produce similar biological toxicity. These findings support the feasibility and potential of VHEE generated by LPA for future clinical applications.