Fractionated FLASH radiation in xenografted lung tumors induced FLASH effect at a split dose of 2 Gy

Yuling Dai; Runcheng Liang; Jianxin Wang; Jing Zhang; Dai Wu; Ri Zhao; Zhaoxing Liu; Faguo Chen

doi:10.1080/09553002.2023.2194403

Fractionated FLASH radiation in xenografted lung tumors induced FLASH effect at a split dose of 2 Gy

Int J Radiat Biol. 2023;99(10):1542-1549. doi: 10.1080/09553002.2023.2194403. Epub 2023 Mar 31.

Authors

Yuling Dai^{1

2}, Runcheng Liang^{1

2}, Jianxin Wang³, Jing Zhang^{1

2}, Dai Wu³, Ri Zhao^{1

2}, Zhaoxing Liu^{1

2}, Faguo Chen^{1

2}

Affiliations

¹ Nuclear and Radiation Frontier Technology Research Center, China Institute for Radiation Protection, Taiyuan, China.
² Shanxi Provincial Key Laboratory for Translational Nuclear Medicine and Precision Protection, Taiyuan, China.
³ Institute of Applied Electronics, China Academy of Engineering Physics, Mianyang, China.

PMID: 36952604
DOI: 10.1080/09553002.2023.2194403

Abstract

Purpose: To explore the minimum split dose of FLASH radiotherapy (FLASH).

Material and methods: Lungs of nude mice were used to verify the capacity of normal tissue sparing of FLASH, while tumor-bearing nude mice were used to evaluate the curative power. Xenografted tumor models were established in Balb/c-nu mice using A549 cells at a concentration of $5 \times 10^{6} / 100 μ L .$ With the same total dose (20 Gy), the dose rate of FLASH was 200 Gy/s when conventional radiotherapy(CONV) was 0.033 Gy/s. Two schemes of FLASH irradiations were applied: single pulse (FLASH1) and ten pulses (FLASH10). Then, according to the different tissue types and irradiation schemes, mice were divided into eight groups: Control-T, CONV-T, FLASH1-T, FLASH10-T (T for tumor) and Control-L, CONV-L, FLASH1-L, FLASH10-L (L for lung). Evaluation of FLASH effect was based on the changes in tumor volume and pathological analysis of tumor and lung tissues before and after irradiation.

Results: Compared to control group, the mean volume of tumors in nude mice increased slowly or decreased after irradiation with both FLASH and CONV (Control-T: 233.6 $\pm$ 55.19 mm³, CONV-T: 146.1 $\pm$ 50.62 mm³, FLASH1-T: 148 $\pm$ 18.83 mm³, FLASH10-T: 119.1 $\pm$ 50.62 mm³, p $\leq .$ 05) . Tumor cells of irradiated groups had similar degrees of dissolution damage and inflammation, while the acute radiation pneumonia induced by FLASH was less severe. The pulmonary pathology of FLASH1-L and FLASH10-L were similar, and only a few neutrophils were observed. In addition to inflammatory cells, slight thickening of alveolar septum and obvious interstitial hemorrhage were also observed in the CONV-L group.

Conclusion: The FLASH effect was successfully reproduced in both single and fractionated irradiation, with 2 Gy being the minimum split dose to achieve the FLASH effect in existing experiments. It is suggested that the transient oxygen depletion might not be the only mechanism behind the FLASH effect.

Keywords: FLASH effect; dose fractionation; oxygen depletion hypothesis; tumor volume; xenografted lung tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Lung / pathology
Lung Neoplasms* / pathology
Lung Neoplasms* / radiotherapy
Mice
Mice, Nude
Oxygen
Radiotherapy Dosage

Substances

Oxygen