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Background <p>Targeted alpha therapy (TAT) utilizing high-LET alpha particles from radionuclides like <sup>225</sup>Ac and <sup>227</sup>Th shows promise in cancer treatment due to their ability to induce dense, localized DNA damage. This study uses the Geant4-DNA Monte Carlo toolkit to simulate DNA damage and evaluate the radiobiological effects of <sup>225</sup>Ac and <sup>227</sup>Th.</p> Results <p>The simulations revealed that both <sup>225</sup>Ac and <sup>227</sup>Th induce significant DNA damage, particularly complex double-strand breaks (DSBs), with <sup>227</sup>Th producing slightly more clustered damage due to its longer decay chain and higher alpha energy. The study also found that both radionuclides exhibited elevated Relative Biological Effectiveness (RBE), especially for complex DSBs. Cell survival analysis showed a sharp decline in viability, consistent with the clustered damage patterns induced by alpha emissions.</p> Conclusions <p>These findings underscore the potential of <sup>225</sup>Ac and <sup>227</sup>Th in targeted radionuclide therapy, particularly for tumors resistant to conventional treatments. The high RBE and complex DNA damage induced by these radionuclides suggest they could enhance therapeutic efficacy when combined with other treatment modalities, such as chemotherapy or immunotherapy, and may benefit patients with tumors exhibiting high DNA repair capacity. This study provides valuable insights for optimizing TAT protocols and advancing the clinical translation of <sup>225</sup>Ac and <sup>227</sup>Th therapies.</p>

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Quantifying DNA strand breaks from targeted alpha emitters 225Ac and 227Th via Geant4-DNA: implications for RBE and cell survival

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月27日

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  • Samaneh Zolghadri,
  • Payman Rafiepour,
  • Hassan Yousefnia

摘要

Background

Targeted alpha therapy (TAT) utilizing high-LET alpha particles from radionuclides like 225Ac and 227Th shows promise in cancer treatment due to their ability to induce dense, localized DNA damage. This study uses the Geant4-DNA Monte Carlo toolkit to simulate DNA damage and evaluate the radiobiological effects of 225Ac and 227Th.

Results

The simulations revealed that both 225Ac and 227Th induce significant DNA damage, particularly complex double-strand breaks (DSBs), with 227Th producing slightly more clustered damage due to its longer decay chain and higher alpha energy. The study also found that both radionuclides exhibited elevated Relative Biological Effectiveness (RBE), especially for complex DSBs. Cell survival analysis showed a sharp decline in viability, consistent with the clustered damage patterns induced by alpha emissions.

Conclusions

These findings underscore the potential of 225Ac and 227Th in targeted radionuclide therapy, particularly for tumors resistant to conventional treatments. The high RBE and complex DNA damage induced by these radionuclides suggest they could enhance therapeutic efficacy when combined with other treatment modalities, such as chemotherapy or immunotherapy, and may benefit patients with tumors exhibiting high DNA repair capacity. This study provides valuable insights for optimizing TAT protocols and advancing the clinical translation of 225Ac and 227Th therapies.