Oxygen consumption measurements at ultra-high dose rate over a wide LET range

Abstract

Background: The role of radiolytic oxygen consumption for the in-vitro "Ultra-High Dose Rate" (UHDR) sparing and in-vivo FLASH effect is subject to active debate, but data on key dependencies such as the radiation quality are lacking.

Purpose: The influence of "dose-averaged Linear Energy Transfer" (LETd) and dose rate on radiolytic oxygen consumption was investigated by monitoring the oxygen concentration during irradiation with electrons, protons, helium, carbon, and oxygen ions at UHDR and "Standard Dose Rates" (SDR).

Methods: Sealed "Bovine Serum Albumin" (BSA) 5% samples were exposed to 15 Gy of electrons and protons, and for the first time helium, carbon, and oxygen ions with LETd values of 1, 5.4, 14.4, 65, and 100.3 keV/µm, respectively, delivered at mean dose rates of either 0.3-0.4 Gy/s for SDR or approximately 100 Gy/s for UHDR. The Oxylite (Oxford Optronics) system allowed measurements of the oxygen concentration before and after irradiation to calculate the oxygen consumption rate.

Results: The oxygen consumption rate was found to decrease with increasing LETd from 0.351 mmHg/Gy for low LET electrons to 0.1796 mmHg/Gy for high LET oxygen ions at SDR and for UHDR from 0.317 to 0.1556 mmHg/Gy, respectively. A higher consumption rate for SDR irradiation compared to the corresponding UHDR irradiation persisted for all particle types.

Conclusion: The measured consumption rates demonstrate a distinct LETd dependence. The obtained dataset, encompassing a wide range of LETd values, could serve as a benchmark for Monte Carlo simulations, which may aid in enhancing our comprehension of oxygen-related mechanisms after irradiations. Ultimately, they could help assess the viability of different hypotheses regarding UHDR sparing mechanisms and the FLASH effect. The found LETd dependence underscores the potential of heavy ion therapy, wherein elevated consumption rates in adjacent normal tissue offer protective benefits, while leaving tumor regions with generally higher "Linear Energy Transfer" (LET) vulnerable.

Keywords: LET; heavy ions; oxygen consumption.

FIGURE 1

Experimental setup at the Mobetron for electron SDR and UHDR irradiation of the Eppendorf tubes.

FIGURE 2

Experimental setup at the HIT beamline for SDR and UHDR irradiation of the Eppendorf tubes with protons, helium, carbon, and oxygen ions.

FIGURE 3

Examples for each particle and dose rate combination of the oxygen concentration over time during a single irradiation. The LETd values are given in the subtitles. p[O₂]_{pre‐irradiation} is the oxygen concentration marked with a black diamond and a dashed line before the radiation has started, while p[O₂]_{post‐irradiation} symbolized with a cross mark and a dotted line hints at the start concentration equilibrium after the dose application. The y‐axis always shows a range of 5 mmHg for better comparability, while the time‐axis is chosen to display the whole consumption process. Due to the 20 s response time of the OxyLite, the drop in oxygen concentration after UHDR irradiation is not instantaneous, but rather slowly decreases as the sensor equilibrates with the depleted medium.

FIGURE 4

Oxygen consumption rate g in BSA 5% against the oxygen concentration prior to the application of 15 Gy for all the various particle and dose rate combinations. Each shade within a given color chosen for one particle represents an independent replicate and thus experiment (Exp.).

FIGURE 5

Fitted g_max values and their standard deviations for every particle type are plotted against their LETd values. The SDR values are marked with a diamond and fitted by the solid line while the UHDR are represented by a cross and fitted by the dashed line. The fit parameters for equation (III) are given with their statistical uncertainties.

FIGURE 6

Difference of g_max values of SDR and UHDR irradiation for the individual particle beams against their LETd. The values are given with their corresponding standard deviations. Additionally, the difference between the fits for the SDR and UHDR g_max values in dependence with LET, as shown in Figure 5, is plotted with its standard deviation represented by the shaded grey area.