Click here to

Session: Radiobiology and Small Animal Systems [Return to Session]

Modeling Differential Tumor and Normal-Tissue Response of FLASH-RT Via Radiolytic Oxygen Depletion and Reactive Oxygen Species

J Ma1*, M Tang1, H Gao2, (1) Shanghai Jiao Tong University, Shanghai, China (2) University of Kansas Medical Center, Kansas City, KS

Presentations

TU-D930-IePD-F3-4 (Tuesday, 7/12/2022) 9:30 AM - 10:00 AM [Eastern Time (GMT-4)]

Exhibit Hall | Forum 3

Purpose: FLASH-RT can improve the sparing of normal tissues while preserving the tumoricidal efficiency, owing to the radiation with ultra-high dose rate. However, the FLASH mechanism remains unclear. A popular FLASH model is based on radiolytic oxygen depletion (ROD), which explains for radiation protection of normal tissues under FLASH. However, ROD does not explain the preservation of tumoricidal efficiency for tumors. This work will develop a FLASH model that can explain the differential tumor and normal-tissue response.

Methods: The FLASH model utilizes reactive oxygen species (ROS) in addition to ROD, and assumes that rapid oxygen consumption during FLASH leads to an increase in ROS. Specifically, the model takes into account that the basic ROS level and degenerate rates of ROS is different in tumor cells and healthy cells. Based on this FLASH model, the surviving fractions of tumor and normal cells are respectively compared between conventional radiotherapy (CONV) and FLASH.

Results: While ROD alone does not distinguish the response of tumors and normal tissues to FLASH, the proposed new FLASH model based on ROD and ROS successfully explained the differential response of tumors and normal tissues to FLASH, i.e., the preserved tumoricidal capability, which cannot be explained by ROD alone, and the extra normal-tissue protection owing to the ultra-high dose rate.

Conclusion: Since ROS levels in tumors are higher than those in normal tissues, tumors are more susceptible to oxygen toxicity caused by high ROS. By incorporating ROS in addition to ROD, the new FLASH model can explain the differential response: preserved lethality of FLASH to tumors and improved protection to normal tissues.

Funding Support, Disclosures, and Conflict of Interest: This research is partially supported by the NIH Grant No. R37CA250921 and a KUCC physicist-scientist recruiting grant.

Keywords

Radiobiology

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): RBio- general

Contact Email

Share: