Evaluation of cumulative absorbed dose in tumors of various sizes regarding ²²⁷Th-based targeted alpha therapy: an in-depth analysis

Producing several alpha-emitting isotopes in the decay chain of ²²⁷Th-based radiopharmaceuticals has increased the complexity of determining the optimal therapeutic dose. This research aims to assess the contribution of each thorium progeny to the cumulative dose in the tumor over time. This assessment will help determine the required injected activity and the appropriate characteristics of a ²²⁷Th-based radiopharmaceutical that can provide an adequate dose to induce sufficient cytotoxicity for effective treatment.

The cumulative dose in tumors of various sizes (with radii of 0.6, 1.2, and 1.8 cm) resulting from the decay of ²²⁷Th was calculated using MCNPX. The radial and temporal distribution of the absorbed dose within the tumor was studied, along with the contribution of each radioisotope to the cumulative dose over time throughout the tumor. Validation of the calculation was performed by determining the cumulative dose of ²²⁷Th-rituximab based on the experimental biodistribution, tumor size and mice weight reported in the literature.

The cumulative dose within the tumor increases over time and is inversely proportional to the tumor's volume. The radial distribution of the cumulative dose within the tumor indicated that ²²⁷Th-based radiopharmaceuticals do not harm the healthy tissue surrounding the tumor.

By taking into account the size of the tumor and the required therapeutic dose, the proposed calculation method can be employed to determine the necessary injected activity and characteristics of a radiopharmaceutical. This includes identifying a suitable retention time and tumor uptake to improve therapeutic outcomes.