HER2 Fab-Tz

HER2 Fab-Tz is a site-specifically modified antibody fragment (Fab) designed for pre-targeted nuclear imaging and therapy of HER2-positive malignancies. The construct consists of a Fab fragment—typically derived from the anti-HER2 monoclonal antibody trastuzumab—conjugated to a tetrazine (Tz) functional group. In a pre-targeting protocol, HER2 Fab-Tz is administered first, allowing it to accumulate at the tumor site and clear from the blood. Subsequently, a small-molecule imaging or therapeutic agent labeled with a trans-cyclooctene (TCO) moiety and a radionuclide (such as Copper-64) is administered. The Tz and TCO groups undergo a rapid, selective, and bioorthogonal Inverse Electron Demand Diels-Alder (IEDDA) reaction in vivo. This approach decouples the slow pharmacokinetics of the antibody fragment from the fast pharmacokinetics of the radioligand, resulting in high tumor-to-background ratios and reduced radiation dose to healthy tissues compared to conventional radioimmunoconjugates.

Other names

tetrazine-modified HER2 FabHER2-targeting Fab-tetrazineHER-2-targeting Fab-tetrazineHER 2-targeting Fab-tetrazine