Abstract
Reception date: August 26, 2023; acceptance date: September 27, 2023.
This is a commentary on the still unsolved problems that are challenging the development of clinically useful 225Ac radiopharmaceuticals for targeted alpha radionuclide therapy (TAT). These issues include the absence of a reliable quality control for establishing the radiochemical purity according to Good Manufacturing Practice (GMP), the ephemeral chemical stability of the bonding between 225Ac and common chelating ligands, and the disruptive recoil effect induced by the α decay of 225Ac with the consequent release of a cascade of free radioactive daughters. The unfavorable nuclear and chemical properties of 225Ac, combined with the absence of gg emissions suitable for monitoring the in vivo pharmacodynamics of 225Ac radiopharmaceuticals, make it arduous to undertake biodistributions in animal models and to obtain realistic dosimetry data. Although 225Ac is currently attracting considerable interest for TAT and a few clinical trials have been reported, it remains questionable whether these studies stand on a solid basis.
Keywords: Actinium-225, Actinium-225-radiopharmaceuticals, Radionuclide therapy, Targeted alpha therapy (TAT), Quality control.
