Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Estimation of DNA Damage in Human Fibroblast Cell from Radiopharmaceuticals by using Monte Carlo Simulation

  • Received : 2023.12.06
  • Accepted : 2023.12.18
  • Published : 2023.12.30
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Abstract

Modelling the damage to DNA molecules by ionizing radiation plays a crucial part in predicting the biological effects of any form of radiation therapy, but the creation of accurate damage models remains scientifically challenging. This study evaluated the frequency and severity of DNA strand breaks caused by direct and indirect radiation effects using the Geant4 DNA simulation toolkit. The DNA itself was represented as a continuous fractal Hilbert curve with a total length of approximately 6.4 Gbp, consisting of straight and twisted chromatin sections placed inside a simplified model of a human fibroblast cell. Using At-211 and Ac-225, both alpha-emitting radionuclides employed under assumption of radiopharmaceutical treatment, the results were compared to those from external irradiation with 1.5 MeV gamma rays. For each Gy of absorbed dose, the strand break yields were 103 ± 10 SSBs/Gbp and 15 ± 4 DSBs/Gbp for At-211, 96 ± 10 SSBs/Gbp and 15 ± 4 DSBs/Gbp for Ac-225, as well as 198 ± 14 SSBs/Gbp and 7 ± 3 DSBs/Gbp for the gamma rays. Thus, the radionuclides exhibited more than double the incidence of DSBs at the expense of SSBs compared to the gamma radiation. By demonstrating the feasibility of adapting the Geant4 DNA toolkit for in silico studies of the radiobiological effects of therapeutic radiopharmaceuticals at the DNA level, this is the first step towards the development of a comprehensive simulation model for determining the relative biological effectiveness of radiopharmaceuticals.

Keywords

Acknowledgement

This work was supported in part by the National Research Foundation of Korea (NRF) funded by the Government of Korea [Ministry of Science and ICT (MSIT)] under Grant 2021-M2E7A2079182. This study was also supported by a grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by the Ministry of Science and ICT (MSIT), Republic of Korea (Grant No. 50461-2024).

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