Laser-plasma acceleration of very high energy electron (VHEE) beams: using ultra high dose rate pulses for in vitro radiobiology studies

Background and Aims: VHEE beams (100-250 MeV) are being considered for the treatment of deep-seated tumors with FLASH-radiotherapy (RT). Laser-plasma acceleration (LPA) through the Laser Wakefield Acceleration (LWFA) mechanismhas been proposed for compactly delivering VHEE beams. LWFA process enables accelerating gradients ordersof magnitude higher than conventional RF-based accelerators. This feature makes laser-driven acceleratorspotential candidates to generate VHEE for future clinical applications. Moreover, LPA provides inherently ultra-high dose rate (UHDR) electrons beams. DNA damage associated with UHDR irradiation is a crucialradiobiological process to understand the underlying mechanisms explaining the sparing of healthy tissueassociated with FLASH-RT. We will present recent results on the dosimetric characterization and stabilitycontrol of our VHEE source based on LWFA at ILIL and its application to in vitro radiobiology measurements. Methods VHEE beams were obtained exploiting LWFA mechanism. Energy and dosimetry information on the beam wereconducted by magnetic spectrometer and EBT3 dosimeter, respectively. To ensure uniform irradiation andaccurate dose measurement, we designed and implemented 3D-printed holders tailored to accommodatebiological sample containers, radiochromic EBT3 dosimeters and a stainless-steel collimator to further refinethe irradiated region. A motorized centering device significantly enhanced the precision of sample positioningwithin the irradiation field. We exposed peripheral blood lymphocytes to VHEE bunches at different doses anddose-rates Results Quite collimated and stable VHEE beams were obtained. Peripheral human blood lymphocytes samples wereeffectively and homogeneously irradiated. The radiobiological response and the dose-dependent data ofchromosomal damage using the cytokinesis-block micronucleus assay was investigated. Conclusions The optimization of our VHEE LPA source and the development of motorized 3D-printed sample holdersenabled irradiation accuracy and enhanced precision in dose measurement. Our preliminary radiobiological findings clearly showed a radiation dose-response in the induction of MN. Asignificant increase in the MN frequency was found from 5cGY to 2Gy as compared to baseline values.