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

Abstract

The high energy of α 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, α radioisotopes can offer a treatment choice to individuals who are not responding to β- or gamma-radiation therapy or chemotherapy drugs. Only a few α-particle emitters are suitable for targeted alpha therapy (TAT) and clinical applications. The majority of available clinical research involves ²²⁵Ac and its daughter nuclide ²¹³Bi. Additionally, the ²²⁵Ac disintegration cascade generates γ 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 ²²⁵Ac, the restricted global accessibility of this radioisotope makes it difficult to conduct extensive clinical trials for many radiopharmaceutical candidates. To boost the availability of ²²⁵Ac, along with its clinical and potential theranostic applications, this review attempts to highlight the fundamental physical properties of this α-particle-emitting isotope, as well as its existing and possible production methods.

Keywords: 225Ac; physical properties; production routes; targeted alpha therapy; theranostic application.

Figure 1

Schematic representation of the biological effects following the use of α-particle emitter radiopharmaceutical for cancer therapy. SSD = Single-Strand Break, DSB = Double-Strand Break, ROS = Reactive Oxygen Species.

Figure 2

The decay chain of ²³³U to ²²⁵Ac and ²¹³Bi.

Figure 3

The principal production routes for ²²⁵Ac.

Figure 4

Schematic representation of the ²¹³Bi elution using the single-column “direct” ²²⁵Ac/²¹³Bi generator.