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

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.

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).

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 RBE_M, i.e. RBE at zero dose, of ²²⁵Ac was 6.91 ± 0.04. In its decay chain, the RBE_M 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.

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.