Description
Purpose: Laser-driven plasma-based particle accelerators beam sources offer (ns-fs) pulses, with spatial resolution, and ultra-high dose rates/shot, presenting promise for radiation modalities such as FLASH radiotherapy. This study aims to present the preliminary radiobiological outcomes of various laser-driven ionizing beams (neutrons, electrons, and protons) operating at the Extreme Light Infrastructure (ELI) facilities, utilizing an optimized zebrafish embryo model for in vivo validation.
Materials and Methods: Zebrafish embryos (24 hpf) were selected for high genetic homology to humans, small size (1 mm), compatible with limited beam size, and suitability for quantifying acute tissue reactions and Relative Biological Effectiveness (RBE).
Experiments were conducted across multiple beamlines:
1. Neutrons (ELI ALPS): 3.2 MeV neutrons generated via 2H(d,n)3H fusion using the 1 kHz SYLOS3 laser. Embryos were exposed to doses (40-380 mGy).
2. Electrons (ELI Beamlines and ELI ALPS): High-repetition-rate electron beams delivering dose rates up to 6 Gy/min and instantaneous peak dose rates exceeding 109 Gy/s.
3. Protons (ELI Beamlines): Petawatt laser-driven protons transported via an 8-meter equiped with beam shaping and dosimetry devices for multi-shot cumulative dose delivery (2.1-2.8 Gy) in the plateau region of the depth-dose curve.
Biological endpoints were evaluated 24 hours post-irradiation using staining for DNA double-strand breaks and for apoptotic cell density measurement, and survival were evaluated during 7 postirradiation days.
Results: Across all modalities, the zebrafish model demonstrated dose-dependent biological responses. Laser-driven neutron irradiation produced DNA damage and apoptosis that matched those of conventional cyclotron-based sources.
Ultra-high-dose-rate electron beams induced dose-dependent effects.
Laser-driven proton delivery showed agreement in biological response with conventional photon and proton beams, with apoptosis more pronounced in the middle of the Spread-Out Bragg Peak.
Conclusion: The study establishes a reliable framework for quantitative, reproducible in vivo radiobiology at relevant doses, validating the therapeutic potential of compact, laser-driven particle sources at ELI facilities.
