Purpose:: Investigations into ultra-high dose rate (UHDR) radiotherapy have dramatically risen because of the observed normal tissue sparing FLASH effect without sacrificing tumor control. The purpose of this study was to provide a direct beamline comparison of protons and electrons to determine where UHDR to conventional dose rates (CDR) changes affect the resultant radiochemistry.
Methods and Materials:: We used well characterized assays of reactive oxygen species (ROS) and oxygen consumption to assess the radiolysis in protein solutions. Three optical reporters related to ROS (CellROX Deep Red, reflects highly reactive radicals; Amplex Red reflects H2O2; and Oxyphor reflects partial pressure loss (ΔpO2)). A Varian ProBeam proton cyclotron and a converted Varian Trilogy electron linac were used for irradiation at both their CDR and UHDR capable level, to assess the assay change per unit dose.
Results:: For both protons and electrons an expected reduction in ROS was noted going from CDR to UHDR, and results interpreted as a reduction in the ratio of UHDR/CDR yield. The CellROX assay showed no difference between beamlines, each showing ~80% reduction in ROS from CDR to UHDR. The Amplex assay showed the largest inter-beamline difference, with ~5% loss using protons vs ~69% loss with electrons, in protein solution. The Oxyphor assay of ΔpO2 showed a small difference in CDR to UHDR with a 23% loss with protons and 43% loss with electrons.
Conclusion:: Interpretation of ROS assays and oxygen consumption is notoriously challenging. These assays might be interpreted by their most activating species’ lifetime. The assay for highly reactive OH●, appeared independent of beamline, whereas the assays for the longer lived H2O2 species and ΔpO2 assay showed differences between beamlines via the UHDR/CDR ratio. This work can be used for FLASH hypothesis testing by comparing these assays to isodose biological FLASH effects in vivo.