The use of F-2-fluorodeoxyglucose (FDG) to label antibody fragments for immuno-PET of pancreatic cancer.

We generated F-labeled antibody fragments for PET imaging using a sortase-mediated reaction to install a transcyclooctene (TCO)-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled-F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields >25%, not decay corrected). The availability of F-2-deoxyfluoroglucose avoids the need for more complicated chemistries used to generate carbon-fluorine bonds. We demonstrate the utility of the method by detecting heterotopic pancreatic tumors in mice by PET, using anti-Class II MHC single domain antibodies. We correlate macroscopic PET images with microscopic two-photon visualization of the tumor. Our approach provides easy access to F-labeled antibodies and their fragments at a level of molecular specificity that complements conventionalF-FDG imaging.