Actinium-225 Decay Chain Delivers Tumor Dose More Efficiently Than Thorium-227 in Simulations

Using Monte Carlo simulations, researchers compared absorbed dose delivery from actinium-225 and thorium-227 in spherical tumors and found that the actinium-225 decay chain, driven by its alpha-emitting progeny, could achieve effective tumor control with a lower injected activity than thorium-227-based alternatives.

The study, published in EJNMMI Physics as an open-access original research article, was conducted by Sepideh Shafiei and Hassan Yousefnia. The authors set out to evaluate the absorbed dose from the full decay chain of actinium-225 in order to optimize therapeutic efficacy and minimize the activity that patients would need to receive, and to determine which of the two radionuclides is the more suitable candidate for clinical application.

Methodologically, the work relies entirely on Monte Carlo simulation using the MCNPX code. The researchers modeled absorbed dose distributions in spherical tumors of three different radii: 0.6, 1.2, and 1.8 centimeters. Rather than treating actinium-225 as a point source of alpha particles, they simulated its complete decay chain, focusing on energy deposition from the key progeny polonium-213, astatine-217, and bismuth-213. The resulting dose profiles for actinium-225-based targeted alpha therapy were then compared directly with those for thorium-227-based therapy.

The simulation results pointed clearly to alpha particles as the dominant destructive force. According to the authors, alpha emissions from the actinium-225 decay chain were the primary contributors to tumor cell destruction, while beta and gamma emissions had minimal impact on the delivered dose.

Tumor size emerged as a decisive variable. The absorbed dose decreased with increasing tumor size across the modeled radii, meaning that smaller lesions received a higher dose per unit of activity than larger ones. Within the decay chain, polonium-213 and astatine-217 were identified as significant contributors to energy deposition, underscoring that the therapeutic value of actinium-225 comes not only from the parent nuclide but from the sequence of daughter decays that follow it.

Perhaps the most practically important result concerned bismuth-213. The simulations showed that retaining this daughter within the tumor was critical for maximizing dose delivery.

Taken together, the results led the authors to conclude that actinium-225 progeny enhance therapeutic efficiency, and that actinium-225-based radiopharmaceuticals offer effective tumor control with lower injected activity compared to thorium-227-based alternatives. In their conclusion, the researchers state that actinium-225-based agents provide superior therapeutic potential over thorium-227-based alternatives, achieving high efficacy with minimal radiotoxicity.

The authors frame the work as a framework rather than a clinical result. By integrating tumor geometry with therapeutic dose requirements, the model is intended to enable determination of optimal injected activity and to guide the development of radiopharmaceuticals with improved retention characteristics. The study underscores the importance of tumor size, radionuclide retention, and progeny-specific contributions in optimizing absorbed dose for targeted alpha therapy.

As with any simulation-based study, the findings describe modeled dose distributions rather than measured outcomes in patients, and the article was shared early as a peer-reviewed, accepted manuscript subject to further edits before the final version of record.

Subject of Research: Monte Carlo simulation of absorbed dose from the actinium-225 decay chain in tumors of varying sizes, compared with thorium-227 for targeted alpha therapy

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

Article References: Shafiei, S., & Yousefnia, H. (2026). Time dependence of absorbed dose in 225Ac-based targeted alpha therapy: a comparative analysis with 227Th. EJNMMI Physics. https://doi.org/10.1186/s40658-026-00946-5

Image Credits: AI Generated

DOI: 10.1186/s40658-026-00946-5

Keywords: actinium-225, thorium-227, targeted alpha therapy, absorbed dose, Monte Carlo simulation, MCNPX, bismuth-213, polonium-213, astatine-217, tumor size, radiopharmaceuticals, decay chain