Biology subjects

Labarbe, R.

Publications and source records attributed to Labarbe, R..

2 recordsLinked to original sources

bioRxiv2025

FLASH or flare: variable intestinal toxicity results in a mouse model following proton pencil beam scanning irradiation on a clinical superconducting synchrocyclotron

Background and aimsUltra-high dose rate (FLASH) irradiation is a promising technique to reduce radiation-induced normal tissue toxicities while preserving antitumor efficacy. We evaluated the feasibility and intestinal sparing potential of FLASH irradiation using a clinical synchrocyclotron-based proton therapy system generating a pulsed beam. Material and methodsC57BL/6J mice received abdominal irradiation (2x2 cm) in transmission mode at FLASH (>60 Gy/s) or conventional (CONV, 0.5 Gy/s) dose rates using a 230 MeV superconducting synchrocyclotron proton pencil beam scanning (PBS) system. Two independent irradiation rounds were performed. Endpoints included 75-day survival, regenerating crypt counts, whole blood counts at day 4, and intestinal wall thickness, cyst-like structures, and cytokine levels at day 75. ResultsIn the first irradiation round, survival after 14.5 Gy FLASH was markedly improved (5/8 survivors) compared to CONV (0/8), whereas in the second round, survival rates were identical (2/7 per group). Overall, pooled data indicated improved survival with 14.5 Gy FLASH. The LD50 was 13.74 Gy in CONV and 14.48 Gy in FLASH mode, corresponding to a FLASH modifying factor of 0.95. FLASH at 14.5 Gy increased regenerating crypt numbers compared to CONV, but only in the first round, supporting survival outcomes. No significant differences were observed in whole blood counts, cytokine profiles, or long-term intestinal structural changes between groups. ConclusionFLASH proton therapy delivered with a clinical synchrocyclotron PBS system can reduce short-term gastrointestinal toxicity in mice. However, inconsistent results across irradiation rounds highlight limitations of this model for reliable FLASH studies.

cancer biology↗

bioRxiv2025

Modelling radio-induced peroxidation of membrane lipids at ultrahigh dose-rate with pulsed beam

1Background and PurposeFLASH radiotherapy, a technique based on delivering large doses in a single fraction at the micro/millisecond timescale, spares normal tissues from late radiation-induced toxicity, in an oxygen-dependent process, whilst keeping full anti-tumor efficiency. The original model of physical-chemical mechanisms [5] underlying the FLASH effect was modified to include a two-compartment (aqueous/lipid) system to take into account key interfacial reactions, and the pulsed nature of the beam. Materials and MethodsThe model predictions were tested by showing a linear correlation between experimentally measured biological outcomes reported in the literature and the final hydroperoxyl lipid [LOOH]f predicted by the model for the different irradiation timing patterns and oxygen concentrations. ResultsThe primary, carbon-centered lipid radical [L*] fades away in less than 5 ms, reproducing the experimental observation. The model predicts a linear correlation of [LOOH]f with the inverse of the square root of the dose rate, as experimentally observed. The predicted [LOOH]f correlates with the recognition ratio of mice irradiated at different dose rates and oxygen concentrations; with zebrafish embryos mean body length for different beam timing structures; with mouse skin toxicity even with dose splitting; and with the survival of mice for different doses per pulse and average dose rates. ConclusionsThe proposed radio-kinetic model attempts to synthesize the experimental results for different beam timing patterns. It successfully shows a correlation between the predicted [LOOH]f and the experimentally observed biological outcomes following irradiation with different dose rates, beam timing structures and oxygen concentrations.

bioinformatics↗