Targeted alpha therapy with Pb or Ac: Change in RBE from daughter migration.

Targeted α-therapy (TAT) could be delivered early to patients who are at a high-risk for developing brain metastases, targeting the areas of the vasculature where tumor cells are penetrating into the brain. We have utilized a Monte Carlo model representing brain vasculature to calculate physical dose and DNA damage from the α-emitters Ac and Pb. The micron-scale dose distributions from all radioactive decay products were modeled in Geant4, including the eV-scale interactions using the Geant4-DNA models. These interactions were then superimposed on an atomic-scale DNA model to estimate strand break yields. In addition to Ac having a higher dose per decay than Pb, it also has a double strand break yield per decay that is 4.7 ± 0.5 times that of Pb. However, the efficacy of both nuclides depends on retaining the daughter nuclei at the target location in the brain vasculature. The relative biological effectiveness (RBE) of Ac and Pb are similar when the entire decay chains are included, with maxima of 2.7 ± 0.6 and 2.5 ± 0.5 (respectively), and RBE values of about 2 to a depth of 80 μm. If the initial daughter is lost, the RBE of Pb is completely reduced to 1 or lower and the RBE of Ac is approximately 2 only for the first 40 μm.