actinium-225-DOTA-pertuzumab

actinium-225-DOTA-pertuzumab (also known as [225Ac]Ac-DOTA-pertuzumab) is a preclinical-stage targeted alpha-particle therapy (TAT) radiopharmaceutical. It consists of the anti-HER2 monoclonal antibody pertuzumab conjugated to the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and radiolabeled with the alpha-emitting radionuclide actinium-225. Pertuzumab specifically binds to domain II of the human epidermal growth factor receptor 2 (HER2), preventing HER2 from pairing with other HER receptors (such as HER3) and blocking downstream signaling. Upon binding to HER2-overexpressing cancer cells, the conjugate delivers highly cytotoxic alpha particles directly to the tumor site, inducing lethal double-strand DNA breaks while minimizing damage to surrounding healthy tissues. Preclinical studies have demonstrated high stability, strong HER2 binding affinity, and promising tumor uptake in HER2-positive ovarian and breast cancer models.

Other names

225Ac-DOTA-pertuzumab225Ac-PD2[225Ac]Ac-DOTA-pertuzumab