Author: Liang Cui, Xingyu Lu, Hang Shang, LingHong Zhou 👨🔬
Affiliation: Southern Medical University 🌍
Purpose: This study examines how varying dose rates of radiotherapy impact normal tissues outside the target area and analyzes the protective effects and regulatory mechanisms of ultra-high dose rate irradiation on these normal tissues.
Methods: Four-week-old female Balb/c mice were injected with 4T1 breast cancer cells and received either FLASH-RT or CONV-RT at a dose of 20Gy two weeks later. EBT-XD film was used to verify the dose. Mice were euthanized two weeks post-radiotherapy, and serum samples, as well as tumor, liver, and kidney tissues, were collected. Biochemical, pathological, and immunological analyses were conducted to assess radiation-induced damage to the tumor and surrounding tissues, along with monitoring mouse survival.
Results: The average dose rates for FLASH-RT and CONV-RT were 625Gy/s and 0.34Gy/s, respectively. The survival rates of mice were similar between the two groups. Both FLASH-RT and CONV-RT demonstrated equivalent efficacy in tumor control. However, the FLASH-RT group exhibited heightened recruitment of immune cells in the liver and kidneys, leading to activated immune protection in normal tissues. Analysis of HE staining showed decreased inflammation in the FLASH-RT group. Serum biochemical analysis indicated abnormal liver resistance function index, renal function index, and lipid index in the FLASH-RT group, along with lower MDA levels suggesting decreased lipid oxidative damage in the distant liver and kidney.
Conclusion: FLASH-RT shows potential advantages by inducing less oxidative damage and inflammation in normal tissues outside the target region while effectively suppressing tumor growth. This may reduce the occurrence of abscopal effects in normal tissues and alleviate radiation toxicity. Furthermore, FLASH-RT’s ability to mitigate lipid oxidative damage and regulate inflammation suggests a potential reduction in abscopal effects and radiation toxicity in normal tissues. This study contributes to a deeper understanding of the mechanisms underlying the FLASH effect.