Tumor cell DNA (targeted by alpha-particle-emitting radiolabeled antibody)

This "target" refers to the direct damage to the DNA of tumor cells mediated by the local emission of high-energy alpha particles from radionuclides attached to tumor-targeting monoclonal antibodies or ligands (radioimmunoconjugates). Upon binding to tumor-specific cell surface antigens, the radioactive payload emits alpha particles that induce irreparable double-stranded DNA breaks within a very short path length, resulting in rapid and localized tumor cell death. This approach is highly cytotoxic to targeted cancer cells with minimal bystander effect on healthy tissue due to the short travel distance of alpha particles. The therapeutic entity is not a single molecular target (like a receptor or enzyme) but the tumor cell DNA as the site of lethal damage following highly localized radiation delivery. This mechanistic focus is used in targeted alpha therapy for various malignancies.

Induction of DNA double-strand breaks by high-linear energy transfer (LET) alpha particles, causing cell death Emission of cytotoxic alpha particles from radionuclide decay locally after delivery by a tumor-targeting antibody or ligand