The Impact of Sub-Millisecond Damage Fixation Kinetics on the In Vitro Sparing Effect at Ultra-High Dose Rate in UNIVERSE

International Journal of Molecular Sciences

Hans Liew¹  Jürgen Debus¹  Amir Abdollahi²  Stewart Mein²  Ivana Dokic²  Andrea Mairani²  Thomas Tessonnier³ 

[1] Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;Division of Molecular and Translational Radiation Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, 69120 Heidelberg, Germany;Heidelberg Ion-Beam Therapy Center (HIT), 69120 Heidelberg, Germany;

关键词: ionizing radiation;    FLASH;    UNIVERSE;    modeling;    ultra-high dose rate;    temporal pulse structure;   

DOI  :  10.3390/ijms23062954

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown