Author: Ramin Abolfath, Alexander Baikalov, Stefan Bartzsch, Nolan M. Esplen, Alan Eduardo Lopez Hernandez, Emil Schueler π¨βπ¬
Affiliation: MD Anderson Cancer Center, PI Experimental Medical Physics, Institute of Radiation Medicine (IRM), Helmholtz Munich, Germany, Howard University, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center π
Purpose: FLASH radiation therapy (FLASH-RT) leverages ultra-high dose rates (UHDR) to spare normal tissue as compared to conventional (CONV)-RT while preserving tumor control; this is termed the FLASH effect. Currently, the mechanism behind the FLASH effect is not fully understood. Hypotheses such as oxygen consumption/depletion and radical-radical interactions at UHDRs have been proposed. However, experimental validation of these hypotheses is challenging due to the need to quantify the yields of short-lived radiolytic species. In this study, we assessed the use of electron paramagnetic resonance (EPR) spectroscopy to characterize the radiation chemistry of UHDR used for FLASH-RT.
Methods: An experimental platform using electron paramagnetic resonance (EPR) spectroscopy with a Bruker Magnettech ESR5000 and spin trap 5,5-Dimethyl-1-Pyrroline-N-Oxide (DMPO) was developed. Samples (2 mL Eppendorf tubes) of DMPO (0.1-100mM) in double-distilled deionized water (100Β΅L) were irradiated with a modified Varian CLINACβs 16 MeV electron beam, capable of delivering UHDR. Chemical kinetics of water radiolysis with DMPO were simulated using KinSim. Dosimetry was performed using alanine pellets and Gafchromic film. Instantaneous dose rates (92x103-75x106 Gy/s) with dose-per-pulse (300Gy-0.37Gy), and pulse repetition frequencies (18Hz-180Hz) were employed. EPR measurement of samples occurred 120 s post-irradiation and the DMPO-OHΛ spectral lines were integrated and compared against a calibration standard to quantify the concentration of DMPO-OHΛ.
Results: Single-pulse irradiation revealed a decreasing G-value (DMPO-OHΛ/Gy) with increasing dose. Same total dose in multi-pulse irradiations confirmed a G-value depency on total dose. The G-value was shown to decrease with increasing pulse number, regardless of mean dose rate. Experimental results generally matched simulation results with the exception of G-value convergence across DPPs at high DMPO, which was not observed experimentally.
Conclusion: An experimental platform for exploring relevant radiolytic reactive species for UHDR irradiations was was used to investigate the relevance of beam parameters in relation to the radiation chemistry of FLASH-RT.