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

Background: 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 Ac and its decay daughters with a Monte Carlo method.

Methods: This study employed the NASIC program to perform microdosimetric simulations of Lu, 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).

Results: The results indicated that variations in radionuclide distribution had a greater impact on the absorbed dose in the cell nucleus. Taking 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, i.e. RBE at zero dose, of Ac was 6.91 ± 0.04. In its decay chain, the RBE was 6.81 ± 0.04 for Fr, 6.67 ± 0.02 for At, 6.43 ± 0.05 for Po, and 5.91 ± 0.09 for Bi. The β-emitting radionuclides Tl and Pb had RBE close to 1.

Conclusions: RBE of each radionuclide in Ac decay chain was evaluated separately with a Monte Carlo track structure code. The RBE of 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 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 Ac-based TAT.