3124 - Local FLASH Radiation Exhibits Double-Edged Effect in Mice Immune System
Presenter(s)
X. Qin1, Y. Li1, P. You1, H. Zha2,3, H. Chen2, J. Wang3, G. Wang4, C. Tian4, F. M. Kong5,6, H. Xiong1, and J. Y. Jin1,4; 1School of Biomedical Engineering, Capital Medical University, Beijing, China, 2Department of Engineering Physics, Tsinghua University, Beijing, China, 3Key Laboratory of Particle and Radiation Imaging of Ministry of Education, Tsinghua University, Beijing, China, 4Beijing Chest Hospital, Capital Medical University, Beijing, China, 5Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong, 6Department of Clinical Oncology, Hong Kong University Shenzhen Hospital, Shenzhen, China
Purpose/Objective(s): Simulation study has shown that local FLASH radiotherapy can spare immune cells in circulating blood due to delivering high dose in relatively smaller blood volumes. This study experimentally investigates the impact of FLASH radiotherapy in immune system in a mouse leg model.
Materials/Methods: The right single hind limb of C57BL/6 mice were irradiated in a single fraction with an electron beam using either 50Gy/s (2Gy, 5Gy, 10Gy, 20Gy, delivery time 0.04s - 0.4s) or 10Gy/s (5Gy, 10Gy, 15Gy, 20Gy, delivery time 0.5s - 1.5s). A total of 80 mice were used in two independent experiments, with five mice per dose group. T lymphocyte subsets (CD3+, CD4+, CD8+) were analyzed in peripheral blood and spleen 1 and 4 days post-irradiation by flow cytometry.
Results: The dose response curve for the subset reduction can be well described by a sigmoid curve as P\left(D\right)=A+\frac{1-A}{1+\funcapply{(\frac{D}{D50})}^\lambda}, where P(D) represents the concentration level of subsets in comparison to the initial level after irradiation of a dose D, A represents the minimal level after a sufficient high dose, and D50 represents the dose when the subsets reduce to the half level of the amplitude. All the lymphocyte subsets show similar behavior in 1 and 4 days. In peripheral blood, A=52.6%, D50=4.8Gy for 50 Gy/s group, while A=31.6%, D50=3.5Gy for 10 Gy/s group, confirming the immune sparing effect by FLASH. Surprisingly, immune cells in spleen also show substantial reduction despite no radiation to the spleen. The behavior is opposite, with A=32.1%, D50=2.7Gy for 50 Gy/s group, and A=38.5%, D50=5.8Gy for 10 Gy/s group. We speculate that cleaning of damaged red blood cell by FLASH radiation in spleen may be responsible for this interesting phenomenon. Simulation study supports our speculation.
Conclusion: We experimentally confirmed the FLASH sparing effect of immune cells in peripheral blood. However, we observed an opposing phenomenon in spleen. The mechanism and clinical significance of this interesting phenomenon in spleen is to be studied in future work.