Does FLASH deplete oxygen? Experimental evaluation for photons, protons, and carbon ions

Abstract

Purpose To investigate experimentally, if FLASH irradiation depletes oxygen within water for different radiation types such as photons, protons, and carbon ions. Methods This study presents measurements of the oxygen consumption in sealed, 3D‐printed water phantoms during irradiation with x‐rays, protons, and carbon ions at varying dose rates up to 340 Gy/s. The oxygen measurement was performed using an optical sensor allowing for noninvasive measurements. Results Oxygen consumption in water only depends on dose, dose rate, and linear energy transfer (LET) of the irradiation. The total amount of oxygen depleted per 10 Gy was found to be 0.04% atm ‐ 0.18% atm for 225 kV photons, 0.04% atm ‐ 0.25% atm for 224 MeV protons, and 0.09% atm ‐ 0.17% atm for carbon ions. Consumption depends on dose rate by an inverse power law and saturates for higher dose rates because of self‐interactions of radicals. Higher dose rates yield lower oxygen consumption. No total depletion of oxygen was found for clinical doses. Conclusions FLASH irradiation does consume oxygen, but not enough to deplete all the oxygen present. For higher dose rates, less oxygen was consumed than at standard radiotherapy dose rates. No total depletion was found for any of the analyzed radiation types for 10 Gy dose delivery using FLASH.

Ultra‐high dose rate electron beams and the FLASH effect: From preclinical evidence to a new radiotherapy paradigm

“…The fundamental physicochemical mechanisms underlying the FLASH effect are currently under investigation; one hypothesis implicating transient local oxygen depletion was first proposed nearly 40 years ago 43,44 . However, direct measurements of such depletion in vivo are difficult to obtain, 45,46 and so most of the evidence to date has been collected via indirect measurements. As one example, reductions in hydrogen peroxide (H 2 O 2 ) in FLASH‐irradiated water have been reported 35 .…”

Spread‐out Bragg peak proton FLASH irradiation using a clinical synchrocyclotron: Proof of concept and ion chamber characterization

“…9 The mechanism of FLASH radiotherapy in sparing normal tissues is not well understood; several hypotheses based on basic radiation physics and chemistry of reactive oxygen species (ROS) and tumor versus normal cell redox metabolism have been proposed in the literature to explain the FLASH effect. [10][11][12][13][14][15] FLASH radiation beams have been achieved using x-rays in a research synchrotron facility, 6 electrons by using medical linear accelerators, [3][4][5]16,17 protons by clinical isochronous cyclotrons [18][19][20][21][22] and a clinical synchrocyclotron. 23 In our previous work, 23 we demonstrated the feasibility of delivering proton beams at a FLASH dose rate in a pristine Bragg peak pattern using a clinical synchrocyclotron as a first step toward realizing an experimental platform for preclinical studies.…”

“…The safety and feasibility of treating a first human patient with FLASH radiotherapy was shown in 2019 9 . The mechanism of FLASH radiotherapy in sparing normal tissues is not well understood; several hypotheses based on basic radiation physics and chemistry of reactive oxygen species (ROS) and tumor versus normal cell redox metabolism have been proposed in the literature to explain the FLASH effect 10‐15 …”

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

“…The implied oxygen depletion detected in the previous model implementation (dashed lines in Figure 3 ) was based on a dose-rate independent oxygen depletion rate constant , as suggested by Petersson et al [ 8 ]. Cao et al (and others [ 19 ]) observed an increased amount of oxygen depleted at SDR (for Cao et al at about 0.1 Gy/s) in comparison to uHDR ( Figure 3 —left panel). To account for this effect, we used an empirical parametrization of g over the applied dose rate (Equation (12)), using the three phenomenological parameters and .…”