Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation

Yuta Shiraishi; Yusuke Matsuya; Tamon Kusumoto; Hisanori Fukunaga

doi:10.1088/1361-6560/ad131b

Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation

Phys Med Biol. 2023 Dec 26;69(1). doi: 10.1088/1361-6560/ad131b.

Authors

Yuta Shiraishi^{1

2}, Yusuke Matsuya^{3

4}, Tamon Kusumoto⁵, Hisanori Fukunaga³

Affiliations

¹ Graduate school of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan.
² Faculty of Health Sciences, Japan Healthcare University, 3-11-1-50 Tsukisamu-higashi, Toyohira-ku, Sapporo, Hokkaido, 062-0053, Japan.
³ Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan.
⁴ Nuclear Science and Engineering Center, Japan Atomic Energy Agency, 2-4 Shirakata, Tokai, Ibaraki, 319-1195, Japan.
⁵ National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.

PMID: 38056015
DOI: 10.1088/1361-6560/ad131b

Abstract

Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s^-1) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s^-1have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed anintegrated microdosimetric-kinetic(IMK)model for UHDR-irradiationenabling the prediction of surviving fraction after UHDR irradiation.Approach.TheIMK model for UHDR-irradiationconsiders the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate.Main results.The estimate by the developed model could successfully reproduce thein vitroexperimental dose-response curve for various cell line types and dose rates.Significance.The developed model would be useful for predicting the biological effects under the UHDR irradiation.

Keywords: DNA damage; FLASH radiotherapy; microdosimetric-kinetic model; surviving fraction; ultra-high dose rate.

MeSH terms

Cell Line
DNA Damage*
DNA Repair*
Kinetics
Radiation Tolerance
Radiotherapy Dosage