Challenges and opportunities in developing Actinium-225 radiopharmaceuticals

Actinium-225 ( 225 Ac) has emerged as a promising therapeutic radioisotope for targeted alpha therapy. It emits net four alpha particles during its decay to stable daughter bismuth-209, rightly called an in-vivo nano-generator . Compared to the worldwide demand of 225 Ac, the amount produced via depleted thorium-229 sources is minimal, making it an expensive radionuclide. However, many research groups are working on optimizing the parameters for the production of 225 Ac via different routes, including cyclotrons, reactors and high-energy linear accelerators. The present review article focuses on the various aspects associated with the development of 225 Ac radiopharmaceuticals. It includes the challenges and opportunities associated with the production methods, labeling chemistry, in-vivo kinetics and dosimetry of 225 Ac radiopharmaceuticals. A brief description is also given about the 225 Ac radiopharmaceuticals at preclinical stages, clinical trials and used routinely.