Multiscale radiobiological assessment of laser-driven very high energy electrons versus conventional electrons

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Abstract

Aim

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 (LINAC). Using in vitro, ex vivo , and in vivo models, we evaluate and compare their potential toxicity on healthy tissues.

Methods

Cell survival, tissue response, and developmental toxicity were assessed across three biological models. In vitro , human fibroblasts (MRC5-hTERT) were used to generate post-irradiation survival curves. Ex vivo , precision-cut lung slices (PCLS) from mice were analyzed for radiation-induced inhibition of cell proliferation. In vivo , zebrafish embryos were used to evaluate developmental toxicity through body length and spinal curvature measurements. VHEE irradiations were performed at 50 MeV using the Salle Jaune LPA (Laboratoire d’Optique Appliquée, France), while CIEE exposures were performed with a 7 MeV conventional LINAC (Institut Curie, France).

Results

In vitro , MRC5-hTERT cells showed no significant difference in radiosensitivity between VHEE and CIEE, with comparable D 10 values (p-value = 0.7). In the ex vivo model, both beams induced a dose-dependent decrease in cell division with no significant inter-beam differences at any dose level (p-value > 0.99). 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 two modalities at matched doses for any measured metric (p-value 0.5).

Conclusion

This study presents the first comprehensive radiobiological evaluation of a laser-driven VHEE beam across 1 multiple biological models. The results demonstrate that VHEE and CIEE irradiations exhibit similar biological toxicity. These findings support the feasibility and potential of VHEE generated with LPA for future clinical applications.

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