Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/ijms23062954
Keywords
ionizing radiation; FLASH; UNIVERSE; modeling; ultra-high dose rate; temporal pulse structure; electrons
Funding
- National Center for Tumor Diseases (NCT) [3.0-2015.22 BioDose]
- Helmholtz International Graduate School for Cancer Research in Heidelberg
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This study extended a biophysical mechanistic model based on the oxygen depletion hypothesis and introduced the temporal pulse structure. Experimental results showed that the model successfully reproduced the fast kinetics of the oxygen effect in irradiated mammalian cells, and it could be used to optimize potential clinical applications and accelerator development.
The impact of the exact temporal pulse structure on the potential cell and tissue sparing of ultra-high dose-rate irradiation applied in FLASH studies has gained increasing attention. A previous version of our biophysical mechanistic model (UNIVERSE: UNIfied and VERSatile bio response Engine), based on the oxygen depletion hypothesis, has been extended in this work by considering oxygen-dependent damage fixation dynamics on the sub-milliseconds scale and introducing an explicit implementation of the temporal pulse structure. The model successfully reproduces in vitro experimental data on the fast kinetics of the oxygen effect in irradiated mammalian cells. The implemented changes result in a reduction in the assumed amount of oxygen depletion. Furthermore, its increase towards conventional dose-rates is parameterized based on experimental data from the literature. A recalculation of previous benchmarks shows that the model retains its predictive power, while the assumed amount of depleted oxygen approaches measured values. The updated UNIVERSE could be used to investigate the impact of different combinations of pulse structure parameters (e.g., dose per pulse, pulse frequency, number of pulses, etc.), thereby aiding the optimization of potential clinical application and the development of suitable accelerators.
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