Description
Very high-energy electrons (VHEEs, 50–250 MeV) are emerging as a promising modality for the treatment of deep-seated tumors due to their favorable penetration depth, dose conformity, and reduced sensitivity to tissue heterogeneities. Their potential application in FLASH radiotherapy further increases interest, as ultra-high dose rates may enhance normal tissue sparing while maintaining tumor control.
Laser Wakefield Acceleration (LWFA) offers a compact approach for VHEE generation, producing ultrashort electron pulses (tens of femtoseconds) with instantaneous dose rates far exceeding those achievable with conventional radiofrequency accelerators. However, the biological effects of such irradiation conditions remain poorly understood.
In this study, the LWFA-driven VHEE source available at the Intense Laser Irradiation Laboratory (ILIL) at INO-CNR in Pisa was comprehensively characterized through measurements of beam energy spectrum, charge per shot, and spatial dose distribution using radiochromic films and spectrometric diagnostics. Human blood leukocytes were irradiated with doses ranging from 0 to 4 Gy at instantaneous dose rates exceeding 10¹² Gy/s. Radiobiological responses were assessed by evaluating both direct and bystander effects through micronucleus formation, telomere length, and mitochondrial DNA copy number. VHEE irradiation induced measurable biological responses, including increased chromosomal damage and telomere shortening. However, compared with conventional X-rays at equivalent doses, VHEEs produced less DNA damage, an effect that may be attributed to the ultra-high instantaneous dose rate per pulse, which could trigger “FLASH-like” mechanisms influencing radical chemistry and DNA damage processing.
These results provide further evidence supporting the unique radiobiological properties of laser-driven VHEEs and contribute to their preclinical validation for future radiotherapy applications. While additional studies are needed to clarify the underlying mechanisms and support clinical translation, laser-plasma accelerators represent a promising route toward next-generation high-dose-rate precision radiotherapy.
