DNA in tumor cells (targeted by lutetium-177 radioligand therapy via binding to prostate-specific membrane antigen-positive cells) (null)

Lutetium-177-based radioligand therapy targets DNA inside tumor cells by delivering beta particle radiation directly after a small molecule, peptide, or antibody ligand binds to PSMA (prostate-specific membrane antigen) highly expressed on the surface of certain cancer cells, especially in prostate cancer. The lutetium-177 isotope emits high-energy beta particles that cause strand breaks in DNA, resulting in tumor cell death while minimizing damage to surrounding healthy tissues due to the limited range of beta emission. This approach requires sufficient PSMA expression on cancer cells, and efficacy can vary based on tumor heterogeneity. Lutetium-177 can also be tracked in the body via co-emitted gamma radiation, enabling a theranostic strategy combining treatment and imaging. Safety concerns focus on radiation exposure to non-target tissues and potential toxicity to organs with physiological PSMA expression, such as salivary glands and kidneys. FDA-approved agents like Pluvicto (lutetium-177 PSMA) and companion PET imaging agents (Gallium-68 PSMA) exemplify current clinical use.

Other names

Prostate-specific membrane antigen (for cell targeting)PSMA-positive tumor cell DNA (mechanistic designation)Lutetium-177 targeted DNA damage (mechanistic)Radioligand therapy target (clinical context)

Beta particle emission from lutetium-177 causes double-strand DNA breaks in PSMA-positive cells, leading to cell death. The drug binds PSMA, delivering the radioactive payload selectively.