University of Pennsylvania
Biochemistry & Biophysics
Dr. Mirna El Khatib holds PhD in organic chemistry from the University of Florida working under the late professor Alan R. Katritzky. Currently she is a research associate and a NIH K25 Fellow in the Department of Biochemistry and Biophysics of the Perelman School of Medicine at the University of Pennsylvania. Her research is focused on the development of advanced probes for optical metabolic imaging and microscopy.

Presenter of 1 Presentation

ULTRAFAST TRACKING OF OXYGEN DYNAMICS DURING PROTON FLASH

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
18:00 - 19:00
Room
Room 2.15
Lecture Time
18:30 - 18:40

Abstract

Background and Aims

Radiotherapy at ultrahigh dose rates (FLASH, >40Gy/sec) compared to conventional radiotherapy (CR; <1 Gy/sec) has been shown to provide an advantage by selective protection of normal versus tumor tissue. Depletion of molecular oxygen causing radioprotection has been proposed to underpin the FLASH effect, however no experimental data have been presented to test this hypothesis. Our goal was to assess the oxygen dynamics during and following proton FLASH versus CR.

Methods

Measurements of oxygen were performed in vitro (solutions in sealed vials) and in vivo in mice (healthy leg muscle and tumors) using the phosphorescence quenching method with probe Oxyphor PtG4 at rates reaching 3 measurements/millisecond during proton irradiation delivered with CR or FLASH dose rates.

Results

In closed systems in vitro the rate of oxygen depletion is oxygen-independent for both FLASH and CR when [O2]>~70 μM. The g-values are lower for FLASH than for CR by ~15%. In vivo oxygen is depleted upon FLASH with rates that correlate with baseline pO2 (partial pressure of oxygen) values throughout the entire pO2 range: at 30-40 mmHg (normal tissue) a 30 Gy FLASH (100 Gy/s) results in ΔpO2 of -8 mmHg, while at 5-7 mmHg (tumor) ΔpO2 is only -1 mmHg.

Conclusions

This study features the first demonstration of the phosphorescence quenching oximetry at ultrafast rates and in the presence of proton radiation. Oxygen depletion by FLASH in vitro was found to be smaller than by CR, and appears to correlate with baseline pO2 values, being greater for normal tissue than for tumors.

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Author Of 1 Presentation

ULTRAFAST TRACKING OF OXYGEN DYNAMICS DURING PROTON FLASH

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
18:00 - 19:00
Room
Room 2.15
Lecture Time
18:30 - 18:40

Abstract

Background and Aims

Radiotherapy at ultrahigh dose rates (FLASH, >40Gy/sec) compared to conventional radiotherapy (CR; <1 Gy/sec) has been shown to provide an advantage by selective protection of normal versus tumor tissue. Depletion of molecular oxygen causing radioprotection has been proposed to underpin the FLASH effect, however no experimental data have been presented to test this hypothesis. Our goal was to assess the oxygen dynamics during and following proton FLASH versus CR.

Methods

Measurements of oxygen were performed in vitro (solutions in sealed vials) and in vivo in mice (healthy leg muscle and tumors) using the phosphorescence quenching method with probe Oxyphor PtG4 at rates reaching 3 measurements/millisecond during proton irradiation delivered with CR or FLASH dose rates.

Results

In closed systems in vitro the rate of oxygen depletion is oxygen-independent for both FLASH and CR when [O2]>~70 μM. The g-values are lower for FLASH than for CR by ~15%. In vivo oxygen is depleted upon FLASH with rates that correlate with baseline pO2 (partial pressure of oxygen) values throughout the entire pO2 range: at 30-40 mmHg (normal tissue) a 30 Gy FLASH (100 Gy/s) results in ΔpO2 of -8 mmHg, while at 5-7 mmHg (tumor) ΔpO2 is only -1 mmHg.

Conclusions

This study features the first demonstration of the phosphorescence quenching oximetry at ultrafast rates and in the presence of proton radiation. Oxygen depletion by FLASH in vitro was found to be smaller than by CR, and appears to correlate with baseline pO2 values, being greater for normal tissue than for tumors.

Hide