Dosimetry at cellular level for the alpha-emitting radionuclides actinium-225, astatine-211 and radium-223 for bone metastasis cells from castration resistant prostate cancer.

Objectives The aim is to evaluate energy deposition in the nucleus and cytoplasm in targeted alpha therapy of metastatic castration-resistant prostate cancer by modeling two cell lines, PC3 (osteolytic) and LNCaP C4-2 (osteoblastic), for actinium-225, astatine-211, and radium-223 and their progeny, using Monte Carlo simulations with the GATE/Geant4 code. Approach We developed single cell and cell clusters models and couple them to Monte Carlo simulations performed on the GATE platform version 9.3, setting the GEANT4-DNA physics list emstandard_opt3_mixed_dna for At-211, Ac-225 and Ra-223 progenies. We considered three radionuclide distributions as a sources: the nucleus, the cytoplasm and the whole cell. Main Results When the nucleus was considered as a target, the S-values (N←N) calculated for At-211, Ac-225 and Ra-223 progenies were significantly higher, within 60-90%, than S-values (N←Cy), demonstrating less influence of cytoplasm internalization. When the cytoplasm was considering as a target, the S-values (Cy←Cy) calculated for At-211, Ac-225 and Ra-223 progeny were significantly higher, within 30-90%, than the S-values (Cy←N). When no progeny migration occurs and the nucleus was considered as the target, the cumulative S-values (N←N) calculated for At-211, Ac-225 and Ra-223 were significantly higher, within 50- 70%, than the S-values (N←N) computed for At-211, Ac-225, and Ra-223. Comparing the cumulative S-values, Ac-225 and Ra-223 therapies is more effective, in terms of deposited energy in a target, than that with At-211. Significance The data presented in this research indicates that Ac-225 therapy may be theoptimum choice due to the energy deposited in the nucleus, as long as the recoil effects and redistribution of progeny are understood. In contrast, At-211 is an alternative to avoid progeny migration. However, to completely analyze the efficacy of radionuclide therapy, other parameters must be considered, such as biological half-life, stability of the transport molecule, progeny migration, excretion pathways, and uptake in different organs. .