Feasibility of FLASH radiobiology with proton and carbon ion beams using LINAC4 and Nuclotron accelerators

Objective.This study evaluates the feasibility of using the high-energy particle accelerators LINAC4 at CERN and the Nuclotron at joint institute for nuclear research for radiobiological experiments under ultra-high dose rate (UHDR) and FLASH-related irradiation conditions with proton and carbon ion beams.Approach.Monte Carlo simulations were performed using the GEANT4 and FLUKA toolkits to model beam transport, dose deposition, and spatial dose characteristics of proton and carbon ion beams generated by the two facilities. Virtual irradiation setups were implemented using water phantoms and digital models of standard cell culture vessels.Main results.The 160 MeV proton beam from LINAC4 and the 430 MeV u^-1carbon ion beam from the Nuclotron achieved high spatial precision and uniform dose distributions within approximately 5 ml water equivalent targets, including within the Bragg peak region. Owing to their pulsed beam structures, comprising millisecond-scale pulses with nanosecond-scale micro bunches, both accelerators can deliver several Gy within short irradiation intervals under UHDR conditions. This enables well-defined delivery relevant forin vitroFLASH studies. In contrast to collimated beams and reproducible temporal structures suitable for investigations aimed at elucidating the biological mechanisms underlying the FLASH effect, which require precise control over dose delivery.Significance.These findings support the suitability of research-dedicated accelerator infrastructures such as LINAC4 and the Nuclotron for preclinical UHDR and FLASH-related radiobiological studies. Their ability to deliver pulsed, high-intensity hadron beams under controlled geometric and temporal conditions fulfils the key physical prerequisites for systematicin vitroinvestigations of UHDR and FLASH effects. By extending FLASH-oriented experimentation beyond clinical environments, this work provides a framework for studies addressing dose-threshold behaviours, tissue-specific responses, and the biological mechanisms underlying the FLASH effect.