Main Session
Sep 28
PQA 03 - Digital Health Innovation and Informatics, Patient Safety & Quality, and Radiation and Cancer Biology

2486 - Does the UHDR Skin Sparing Effect Maintain Efficacy in the Awake Murine Model? Investigation of Competing Irradiation Conditions

10:45am - 12:00pm ET
Poster Hall - Exhibit Hall A
Screen: 5
POSTER

Presenter(s)

David Hunter, MS Headshot
David Hunter, MS - Dartmouth College, Hanover, NH

D. I. Hunter1, A. Ilina2, B. Petusseau2, A. Tavakkoli3, J. Gunn2, D. J. Gladstone4, and B. W. Pogue2; 1Thayer School of Engineering, Dartmouth College, Hanover, NH, 2Thayer School of Engineering at Dartmouth College, Hanover, NH, 3Dartmouth Geisel School of Medicine, Lebanon, NH, 4Geisel School of Medicine at Dartmouth & Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH

Purpose/Objective(s):

This study aimed to investigate the radiation response between ultra-high dose rate (UHDR) and conventional dose rate (CDR) deliveries in awake and anesthetized mice, and to quantify anesthesia driven oxygenation changes between awake and anesthetized cohorts. Recent studies have shown that the UHDR sparing effect is modulated by changes in oxygenation conditions driven by anesthesia, though a comparison to awake mice has yet to be quantified.

Materials/Methods:

Male B6 (n=40) and Albino B6 (n=41) mice were split into UHDR and conventional dose rate (CDR) cohorts, and further stratified by anesthesia condition (awake or anesthetized) at the time of irradiation into UHDR + isoflurane (n = 20), CDR + isoflurane (n = 20), UHDR + awake (n = 21), and CDR + awake (n = 20) groups. Prior to irradiation, mice flanks were shaved, and 50 uL of 200 uM Oxyphor PdG4 was administered systemically via a retro-orbital injection. Mice were irradiated on an IntraOp Mobetron linear accelerator using electrons (9 MeV) to a prescribed surface dose of 25 Gy, delivered at 375 Gy/s. CDR cohort mice were irradiated at a dose rate of 0.17 Gy/s.

Anesthetized mice were induced using isoflurane mixed with room air (3.0% Iso at 500 ml/min) and maintained during irradiations (2.5% Iso at 250 ml/min). Mice in the awake cohort were restrained within an enclosure to prevent movement during irradiation, with their left hind leg extended from the enclosure and positioned under the 1.6cm circular field. Tissue pO2 was measured during irradiation using the OxyLED system in both awake and anesthetized groups. Post irradiation, mice were imaged once daily using a white-light imaging system for 30 days, with individual mice removed from study once extensive limb breakdown had occurred. Skin damage was graded retrospectively by two trained individuals blinded to the experiment conditions.

Results:

Anesthetized UHDR mice showed significantly less damage than anesthetized CDR mice (p<0.001) over the course of the study. However, no significant sparing was shown between awake cohorts. This effect was primarily driven by a response in the UHDR cohorts, with CDR cohort damage remaining similar between anesthesia conditions. Statistically significant differences were observed in the partial pressure of oxygen in the irradiated tissue between awake and anesthetized cohorts (32.99±6.73 mmHg, 17.69±5.04 mmHg).

Conclusion:

No differences were observed at a dose level of 25 Gy in awake male B6 and albino B6 mice, while a UHDR sparing effect was shown to be present in anesthetized mice at an equivalent dose level. In line with prior work evaluating the effects of anesthetized carbogen (95% O2, 5% CO2) breathing during UHDR irradiations in male mice, the absence of an observed UHDR sparing effect may be due to an elevation in tissue pO2. However, this study presents early work not accounting for a differential in the stress response of irradiated, awake mice, which may increase local tissue oxygenation as a result of increased respiration and heart rate.