Time dependence of absorbed dose in 225Ac-based targeted alpha therapy: a comparative analysis with 227Th

This study evaluates the absorbed dose from the decay chain of Actinium-225 ( 225 Ac) to optimize therapeutic efficacy and minimize the required injected activity for targeted alpha therapy (TAT). Additionally, it compares the cumulative absorbed doses of 225 Ac and Thorium-227 ( 227 Th) therapies to identify the more suitable radionuclide for clinical application. Monte Carlo simulations (MCNPX) were used to model absorbed dose distributions in spherical tumors of varying radii (0.6, 1.2, and 1.8 cm). The full decay chain of 225 Ac was simulated, focusing on energy deposition from key progeny: Polonium-213 (²¹³Po), Astatine-217 ( 217 At), and Bismuth-213 (²¹³Bi). Absorbed dose profiles for 225 Ac-based TAT were compared with 227 Th-based therapy. Simulation results showed that alpha particles from the 225 Ac decay chain were the primary contributors to tumor cell destruction, while beta and gamma emissions had minimal impact. The absorbed dose decreased with increasing tumor size, and ²¹³Po and 217 At were significant contributors to energy deposition. Retaining ²¹³Bi within the tumor was critical for maximizing dose delivery. Overall, the 225 Ac progeny enhanced therapeutic efficiency, suggesting that 225 Ac -based radiopharmaceuticals offer effective tumor control with lower injected activity compared to 227 Th-based alternatives. This study underscores the importance of tumor size, radionuclide retention, and progeny-specific contributions in optimizing absorbed dose for TAT. The proposed framework integrates tumor geometry with therapeutic dose requirements, enabling the determination of optimal injected activity and the development of radiopharmaceuticals with improved retention characteristics. These findings suggest that 225 Ac-based agents provide superior therapeutic potential over 227 Th-based alternatives, achieving high efficacy with minimal radiotoxicity.