Dataset Information

Ultrafast Tracking of Oxygen Dynamics During Proton FLASH.

ABSTRACT:

Purpose

Radiation therapy delivered at ultrafast dose rates, known as FLASH RT, has been shown to provide a therapeutic advantage compared with conventional radiation therapy by selectively protecting normal tissues. Radiochemical depletion of oxygen has been proposed to underpin the FLASH effect; however, experimental validation of this hypothesis has been lacking, in part owing to the inability to measure oxygenation at rates compatible with FLASH.

Methods and materials

We present a new variant of the phosphorescence quenching method for tracking oxygen dynamics with rates reaching up to ∼3.3 kHz. Using soluble Oxyphor probes we were able to resolve, both in vitro and in vivo, oxygen dynamics during the time of delivery of proton FLASH.

Results

In vitro in solutions containing bovine serum albumin the O₂ depletion g values (moles/L of O₂ depleted per radiation dose, eg, µM/Gy) are higher for conventional irradiation (by ∼13% at 75 µM [O₂]) than for FLASH, and in the low-oxygen region (<25 µM [O₂]) they decrease with oxygen concentration. In vivo, depletion of oxygen by a single FLASH is insufficient to achieve severe hypoxia in initially well-oxygenated tissue, and the g values measured appear to correlate with baseline oxygen levels.

Conclusions

The developed method should be instrumental in radiobiological studies, such as studies aimed at unraveling the mechanism of the FLASH effect. The FLASH effect could in part originate from the difference in the oxygen dependencies of the oxygen consumption g values for conventional versus FLASH RT.

SUBMITTER: El Khatib M

PROVIDER: S-EPMC9250619 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Ultrafast Tracking of Oxygen Dynamics During Proton FLASH.

El Khatib Mirna M Van Slyke Alexander L AL Velalopoulou Anastasia A Kim Michele M MM Shoniyozov Khayrullo K Allu Srinivasa Rao SR Diffenderfer Eric E EE Busch Theresa M TM Wiersma Rodney D RD Koch Cameron J CJ Vinogradov Sergei A SA

International journal of radiation oncology, biology, physics 20220318 3

<h4>Purpose</h4>Radiation therapy delivered at ultrafast dose rates, known as FLASH RT, has been shown to provide a therapeutic advantage compared with conventional radiation therapy by selectively protecting normal tissues. Radiochemical depletion of oxygen has been proposed to underpin the FLASH effect; however, experimental validation of this hypothesis has been lacking, in part owing to the inability to measure oxygenation at rates compatible with FLASH.<h4>Methods and materials</h4>We prese ...[more]

PMID: 35314293

Similar Datasets

Project description:PurposeDelivery of radiation at ultrahigh dose rates (UHDRs), known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared with tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypotheses being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation.Methods and materialsOxygen measurements were performed in vitro and in vivo using the phosphorescence quenching method and a water-soluble molecular probe Oxyphor 2P. The changes in oxygen per unit dose (G-values) were quantified in response to irradiation by 10 MeV electron beam at either UHDR reaching 300 Gy/s or conventional radiation therapy dose rates of 0.1 Gy/s.ResultsIn vitro experiments with 5% bovine serum albumin solutions at 23°C resulted in G-values for oxygen consumption of 0.19 to 0.21 mm Hg/Gy (0.34-0.37 μM/Gy) for conventional irradiation and 0.16 to 0.17 mm Hg/Gy (0.28-0.30 μM/Gy) for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3 ± 0.3 mm Hg in normal tissue and 1.0 ± 0.2 mm Hg in tumor tissue (P < .00001), whereas no decrease in oxygen was observed from a single fraction of 20 Gy applied in conventional mode.ConclusionsOur observations suggest that oxygen depletion to radiologically relevant levels of hypoxia is unlikely to occur in bulk tissue under FLASH irradiation. For the same dose, FLASH irradiation induces less oxygen consumption than conventional irradiation in vitro, which may be related to the FLASH sparing effect. However, the difference in oxygen depletion between FLASH and conventional irradiation could not be quantified in vivo because measurements of oxygen depletion under conventional irradiation are hampered by resupply of oxygen from the blood.

Dataset Information

Ultrafast Tracking of Oxygen Dynamics During Proton FLASH.

Purpose

Methods and materials

Results

Conclusions

Publications

Ultrafast Tracking of Oxygen Dynamics During Proton FLASH.

Similar Datasets

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