In Vivo Evaluation Of Free And Chelated Accelerator-Produced Actinium-225 - Radiation Dosimetry And Toxicity Results

Background and Objective: The demand for the alpha-emitting radionuclide Actinium-225 (Ac-225) for use in radionuclide therapy is growing. Producing Ac-225 using high energy linear accelerators, cyclotrons or photoinduction could increase its supply. One potential problem with accelerator produced Ac-225 using Thorium-232 targets is the presence in final product of 0.1-0.3% by activity of the long-lived Ac-227 impurity at the end of irradiation. It is important to comprehensively evaluate the behavior of accelerator-produced Ac-225 in vivo before using it in pre-clinical and clinical applications.Methods: Biodistribution of accelerator-produced Ac-225 in acetate (free) and DOTA complex forms was performed in male and female CD-1 mice. The biodistribution data was used for radiation dosimetry calculations. The toxicity studies of free Ac-225 were conducted in CD-1 mice at 1.036 and 2.035 kBq/g body weight. Blood counts, body weight and post-mortem histology were evaluated.Results: In both genders, there was a pronounced uptake of free Ac-225 in the liver when compared to Ac-225-DOTA which resulted in 200 and 50 times higher liver radiation dose for free Ac-225 in male and female mice, respectively. Ac-227 contribution to radiation dose delivered by Ac-225 was calculated to be negligible. Mice given free Ac-225 did not lose weight, had only transient effect on their blood counts and showed no histological damage to the liver and bone marrow.Conclusion: Our biodistribution/dosimetry/toxicity study of accelerator-produced Ac-225 demonstrated the patterns very similar to Th-229-derived Ac-225. We conclude that accelerator-produced Ac-225 is suitable for the developmental work of targeted radionuclide therapy.