[225Ac]Ac-Macropa-SEZ6-Ab

[225Ac]Ac-Macropa-SEZ6-Ab is a preclinical-stage targeted alpha-particle radioimmunotherapeutic developed by the National Cancer Institute (NCI) and the National Institutes of Health (NIH) for the treatment of small cell lung cancer (SCLC) and other neuroendocrine malignancies. The agent consists of a humanized monoclonal antibody targeting seizure protein 6 homolog (SEZ6), conjugated via a macropa chelator to the alpha-emitting radionuclide actinium-225 ([225Ac]Ac). SEZ6 is a cell surface type I transmembrane protein highly expressed in SCLC and other neuroendocrine tumors, with minimal expression in normal tissues. Upon binding to SEZ6 on tumor cells, the radioconjugate is rapidly internalized, delivering localized, highly cytotoxic alpha-particle radiation that induces DNA double-strand breaks and cell death. Preclinical studies have demonstrated that [225Ac]Ac-Macropa-SEZ6-Ab induces complete tumor regression in SCLC xenograft models, and its therapeutic efficacy can be further potentiated when combined with DNA damage response inhibitors such as the ATR inhibitor berzosertib.

Other names

225Ac-Macropa-SEZ6-Ab[225Ac]Ac-macropa-SEZ6-Abactinium-225 macropa-SEZ6-Abactinium225 macropa-SEZ6-Abactinium 225 macropa-SEZ6-Abactinium-225-labeled macropa-SEZ6-Abactinium225-labeled macropa-SEZ6-Abactinium 225-labeled macropa-SEZ6-Ab