225Ac-L1

225Ac-L1 is a targeted alpha-therapy (TAT) radiopharmaceutical designed for the treatment of prostate cancer and other solid tumors expressing Prostate-Specific Membrane Antigen (PSMA). The compound consists of the alpha-emitting radionuclide Actinium-225 conjugated to a small-molecule ligand (L1) that utilizes a Glu-urea-Lys binding motif to achieve high-affinity targeting of PSMA. Upon binding to the target antigen on the cell surface and subsequent internalization, the Actinium-225 releases high-linear energy transfer (LET) alpha particles. These particles induce lethal double-stranded DNA breaks within the tumor cells, leading to cell death while minimizing radiation exposure to surrounding healthy tissues due to the short range of alpha emission. Preclinical studies have demonstrated its efficacy in inhibiting tumor growth in PSMA-positive models of prostate cancer and renal cell carcinoma, showing superior survival benefits in micrometastatic models compared to beta-emitting counterparts like 177Lu-L1.

Other names

[225Ac]Ac-L1Actinium-225 L1Actinium225 L1Actinium 225 L1