Background and Objective: The demand for the alpha-emitting radionuclide Actinium-225
(225Ac) for use in radionuclide therapy is growing. Producing 225Ac using high energy linear accelerators,
cyclotrons or photoinduction could increase its supply. One potential problem with accelerator
produced 225Ac using Thorium-232 targets is the presence in final product of 0.1-0.3% by activity of the
long-lived 227Ac impurity at the end of irradiation. It is important to comprehensively evaluate the behavior
of accelerator-produced 225Ac in vivo before using it in pre-clinical and clinical applications.
Methods: Biodistribution of accelerator-produced 225Ac 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 225Ac 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 225Ac in the liver when compared to
225Ac-DOTA which resulted in 200 and 50 times higher liver radiation dose for free 225Ac in male and
female mice, respectively. 227Ac contribution to radiation dose delivered by 225Ac was calculated to be
negligible. Mice given free 225Ac 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 225Ac demonstrated
the patterns very similar to 229Th-derived 225Ac. We conclude that accelerator-produced 225Ac is suitable
for the developmental work of targeted radionuclide therapy.