A review of recent advancements in Actinium-225 labeled compounds and biomolecules for therapeutic purposes

Abstract

In nuclear medicine, cancers that cannot be cured or can only be treated partially by traditional techniques like surgery or chemotherapy are killed by ionizing radiation as a form of therapeutic treatment. Actinium-225 is an alpha-emitting radionuclide that is highly encouraging as a therapeutic approach and more promising for targeted alpha therapy (TAT). Actinium-225 is the best candidate for tumor cells treatment and has physical characteristics such as high (LET) linear energy transfer (150 keV per μm), half-life (t_1/2 = 9.92d), and short ranges (400-100 μm) which prevent the damage of normal healthy tissues. The introduction of various new radiopharmaceuticals and radioisotopes has significantly assisted the advancement of nuclear medicine. Ac-225 radiopharmaceuticals continuously demonstrate their potential as targeted alpha therapeutics. ²²⁵ Ac-labeled radiopharmaceuticals have confirmed their importance in medical and clinical areas by introducing [²²⁵ Ac]Ac-PSMA-617, [²²⁵ Ac]Ac-DOTATOC, [²²⁵ Ac]Ac-DOTA-substance-P, reported significantly improved response in patients with prostate cancer, neuroendocrine, and glioma, respectively. The development of these radiopharmaceuticals required a suitable buffer, incubation time, optimal pH, and reaction temperature. There is a growing need to standardize quality control (QC) testing techniques such as radiochemical purity (RCP). This review aims to summarize the development of the Ac-225 labeled compounds and biomolecules. The current state of their reported resulting clinical applications is also summarized as well.

Keywords: Actinium-225; antibodies; cancer treatment; radiolabeled peptides; radiopharmaceuticals; targeted alpha therapy (TAT).