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

Area of Science:

• Nuclear Medicine
• Radiation Oncology
• Medical Physics

Background:

• Targeted alpha therapy (TAT) uses high-linear energy transfer (LET) alpha particles for cancer treatment.
• Radionuclides like Actinium-225 (²²⁵Ac) and Thorium-227 (²²⁷Th) induce dense, localized DNA damage.

Purpose of the Study:

• Simulate DNA damage induced by ²²⁵Ac and ²²⁷Th using Geant4-DNA.
• Evaluate the radiobiological effects and relative biological effectiveness (RBE) of these alpha emitters.

Main Methods:

• Monte Carlo simulations with the Geant4-DNA toolkit.
• Analysis of DNA damage patterns, including complex double-strand breaks (DSBs).
• Cell survival analysis to assess biological impact.

Main Results:

• Both ²²⁵Ac and ²²⁷Th induce significant DNA damage, with ²²⁷Th causing more clustered damage.
• Elevated RBE observed for both radionuclides, particularly for complex DSBs.
• Cell viability sharply decreased, correlating with induced clustered DNA damage.

Conclusions:

• ²²⁵Ac and ²²⁷Th show significant potential for targeted radionuclide therapy, especially for resistant tumors.
• High RBE and complex DNA damage suggest enhanced efficacy when combined with other therapies.
• Findings support optimization of TAT protocols and clinical translation of ²²⁵Ac and ²²⁷Th.