Jacob P Sunnerberg, Armin D Tavakkoli, Arthur F Petusseau, Noah J Daniel, Austin M Sloop, Wilson A Schreiber, Jiang Gui, Rongxiao Zhang, Harold M Swartz, P Jack Hoopes, David J Gladstone, Sergei A Vinogradov, Brian W Pogue
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引用次数: 0
Abstract
Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.
Methods and materials: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator. Oxyphor PdG4 was administered into the subcutaneous tissue of the flank skin 1 hour before irradiation. Skin oxygen tension (pO2) was manipulated by adjusting oxygen content in the inhaled gas mixture and/or by vasculature compression. A skin surface radiation dose of 19.8 ± 0.3 Gy was verified using a calibrated semiconductor diode dosimeter. Dose rate was varied across the UHDR range by changing linear accelerator cone length and pulse repetition frequency.
Results: The decrease in pO2 per unit dose during radiation delivery, termed oxygen consumption g-value (gO2, mmHg/Gy), was significantly influenced by tissue oxygen levels in the range 0 to 65 mmHg under UHDR conditions. Within the 0 to 20 mmHg range, gO2 exhibited a sharp increase with rising baseline pO2, plateauing at 0.26 mmHg/Gy. Dose rate variations (mean values, 25-1170 Gy/s; per pulse doses of 2.5-9.8 Gy) were explored by varying both cone length and pulse repetition frequency (10-120 Hz) with no significant changes in gO2. Conventional dose rate irradiation resulted in no discernible changes in pO2.
Conclusions: The results show significant differences in the radiation-chemical effects of UHDR radiation between hypoxic and well-oxygenated tissues. Similar trends between earlier published in vitro and in vivo experiments presented herein suggest the chemical mechanisms driving the dependencies of gO2 on pO2 are similar, potentially underpinning the FLASH effect. Importantly, significant variations in baseline pO2 were observed in animals kept under identical conditions, underscoring the necessity to control and monitor tissue oxygen levels for preclinical investigations and future clinical applications of FLASH radiation therapy.
期刊介绍：
International Journal of Radiation Oncology • Biology • Physics (IJROBP), known in the field as the Red Journal, publishes original laboratory and clinical investigations related to radiation oncology, radiation biology, medical physics, and both education and health policy as it relates to the field.
This journal has a particular interest in original contributions of the following types: prospective clinical trials, outcomes research, and large database interrogation. In addition, it seeks reports of high-impact innovations in single or combined modality treatment, tumor sensitization, normal tissue protection (including both precision avoidance and pharmacologic means), brachytherapy, particle irradiation, and cancer imaging. Technical advances related to dosimetry and conformal radiation treatment planning are of interest, as are basic science studies investigating tumor physiology and the molecular biology underlying cancer and normal tissue radiation response.
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