Targeted Alpha Therapy: All We Need to Know about ²²⁵Ac's Physical Characteristics and Production as a Potential Theranostic Radionuclide

The high energy of alpha emitters, and the strong linear energy transfer that goes along with it, lead to very efficient cell killing through DNA damage. Moreover, the degree of oxygenation and the cell cycle state have no impact on these effects. Therefore, alpha radioisotopes can offer a treatment choice to individuals who are not responding to beta- or gamma-radiation therapy or chemotherapy drugs. Only a few alpha-particle emitters are suitable for targeted alpha therapy (TAT) and clinical applications. The majority of available clinical research involves Ac-225 and its daughter nuclide Bi-213. Additionally, the Ac-225 disintegration cascade generates gamma decays that can be used in single-photon emission computed tomography (SPECT) imaging, expanding the potential theranostic applications in nuclear medicine. Despite the growing interest in applying Ac-225, the restricted global accessibility of this radioisotope makes it difficult to conduct extensive clinical trials for many radiopharmaceutical candidates. To boost the availability of Ac-225, along with its clinical and potential theranostic applications, this review attempts to highlight the fundamental physical properties of this alpha-particle-emitting isotope, as well as its existing and possible production methods.