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Background <p><sup>225</sup>Ac is a radionuclide that can be utilized in targeted alpha therapy (TAT). To accurately assess the absorbed dose and radiation effects in TAT, it is necessary to calculate the relative biological effectiveness (RBE). This study aims to calculate the RBE of <sup>225</sup>Ac and its decay daughters with a Monte Carlo method.</p> Methods <p>This study employed the NASIC program to perform microdosimetric simulations of <sup>177</sup>Lu, <sup>225</sup>Ac and its decay daughters in a cell population. Absorbed doses and lineal energy spectra in the cell nucleus were obtained for eight different radionuclides, three different cells, and six radionuclide spatial distribution. The RBE was then calculated using a modified stochastic microdosimetric kinetic model (mSMKM).</p> Results <p>The results indicated that variations in radionuclide distribution had a greater impact on the absorbed dose in the cell nucleus. Taking <sup>225</sup>Ac in V79 cells as an example, the maximum differences in RBE and absorbed dose due to different distributions were 10% and 80%, respectively. For V79 cells, with a uniform distribution of radionuclides within the cell, the RBE<sub>M</sub>, i.e. RBE at zero dose, of <sup>225</sup>Ac was 6.91 ± 0.04. In its decay chain, the RBE<sub>M</sub> was 6.81 ± 0.04 for <sup>221</sup>Fr, 6.67 ± 0.02 for <sup>217</sup>At, 6.43 ± 0.05 for <sup>213</sup>Po, and 5.91 ± 0.09 for <sup>213</sup>Bi. The β-emitting radionuclides <sup>209</sup>Tl and <sup>209</sup>Pb had RBE close to 1.</p> Conclusions <p>RBE of each radionuclide in <sup>225</sup>Ac decay chain was evaluated separately with a Monte Carlo track structure code. The RBE of <sup>225</sup>Ac and its decay daughters was found to be influenced by absorbed dose, radionuclide distribution, and cell type. The intracellular distribution of radionuclides had influence on the magnitude of RBE, but was less significant than its impact on the absorbed dose. Additionally, there were differences in the RBE of each radionuclide in the <sup>225</sup>Ac decay chain that could not be neglected. These findings contribute to the calculation of RBE-weighted doses and the assessment of biological effects in <sup>225</sup>Ac-based TAT.</p>

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Evaluation of relative biological effectiveness of 225Ac and its decay daughters with Monte Carlo track structure simulations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月7日

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  • Ziyi Hu,
  • Shuiyin Qu,
  • Hongming Liu,
  • Yunhao Zhang,
  • Shuchang Yan,
  • Ankang Hu,
  • Rui Qiu,
  • Zhen Wu,
  • Hui Zhang,
  • Junli Li

摘要

Background

225Ac is a radionuclide that can be utilized in targeted alpha therapy (TAT). To accurately assess the absorbed dose and radiation effects in TAT, it is necessary to calculate the relative biological effectiveness (RBE). This study aims to calculate the RBE of 225Ac and its decay daughters with a Monte Carlo method.

Methods

This study employed the NASIC program to perform microdosimetric simulations of 177Lu, 225Ac and its decay daughters in a cell population. Absorbed doses and lineal energy spectra in the cell nucleus were obtained for eight different radionuclides, three different cells, and six radionuclide spatial distribution. The RBE was then calculated using a modified stochastic microdosimetric kinetic model (mSMKM).

Results

The results indicated that variations in radionuclide distribution had a greater impact on the absorbed dose in the cell nucleus. Taking 225Ac in V79 cells as an example, the maximum differences in RBE and absorbed dose due to different distributions were 10% and 80%, respectively. For V79 cells, with a uniform distribution of radionuclides within the cell, the RBEM, i.e. RBE at zero dose, of 225Ac was 6.91 ± 0.04. In its decay chain, the RBEM was 6.81 ± 0.04 for 221Fr, 6.67 ± 0.02 for 217At, 6.43 ± 0.05 for 213Po, and 5.91 ± 0.09 for 213Bi. The β-emitting radionuclides 209Tl and 209Pb had RBE close to 1.

Conclusions

RBE of each radionuclide in 225Ac decay chain was evaluated separately with a Monte Carlo track structure code. The RBE of 225Ac and its decay daughters was found to be influenced by absorbed dose, radionuclide distribution, and cell type. The intracellular distribution of radionuclides had influence on the magnitude of RBE, but was less significant than its impact on the absorbed dose. Additionally, there were differences in the RBE of each radionuclide in the 225Ac decay chain that could not be neglected. These findings contribute to the calculation of RBE-weighted doses and the assessment of biological effects in 225Ac-based TAT.