Progress of 225Ac-Labelled Radiopharmaceuticals for Cancer Treatment

Abstract

225Ac with the advantages of longer half-life(10 d), shorter range(<100 μm) and high energy deposition(80-100 keV/μm) compared with other medical isotopes, is one of the most important alpha-emitting nuclides. The α particles emitted by 225Ac can cause DNA double-strand breaks in tumor cells, which is more favourable in clinical application. This review delineates the decay characteristics and production methodologies of 225Ac, alongside detailing the conjugation of 225Ac with target-specific ligands through various chelation strategies. It encapsulates the advancements in research and clinical applications of 225Ac-labeled compounds, including 225Ac-prostate-specific membrane antigen(PSMA)-617, 225Ac-PSMA-I&T, 225Ac-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)-SP, and 225Ac-1,4,7,10-tetraazacyclododecane-N, N', N″, N'″-tetraacetic acid d-phenylalanine1-tyrosine3-octreotide(DOTATE), in the therapeutic regimes for prostate cancer, gliomas, breast carcinoma, and pulmonary malignancies. The difficulties and challenges of 225Ac-labelled radiopharmaceutical are also forecasted, in order to provide reference for the research and application of 225Ac-labelled radiopharmaceuticals in the treatment of malignant tumors.

Keywords

• 225ac
• alpha-emitting nuclide
• therapy
• cancer