Due to their target specificity, antibody-drug conju-gates -monoclonal antibodies conjugated to a cytotoxic moiety -are efficient therapeutics that can kill malignant cells overexpressing a target gene. Linking an antibody with radioisotopes (radioimmunoconjugates) enables powerful diagnostics and/or closely related therapeutic applications, depending on the isotope. To generate site-specific radioimmunoconjugates, we utilized genetic code expansion and subsequent conjugation by inverse electron-demand Diels-Alder cyclo-addition reactions. We show that, using this approach, site-specific labeling of trastuzumab with either zirconium-89 (Zr-89) for diagnostics or lutetium-177 (Lu-177) for therapeutics yields efficient radioimmunoconju-gates. Positron emission tomography imaging revealed a high accumulation of site-specifically Zr-89-labeled trastuzumab in tumors after 24 h and low accumulation in other organs. The corresponding Lu-177-trastuzumab radioimmunoconjugates were comparably distributed in vivo.
展开▼
