Use of ¹⁸F-2-Fluorodeoxyglucose to Label Antibody Fragments for Immuno-Positron Emission Tomography of Pancreatic Cancer

Abstract

We generated ¹⁸F-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-¹⁸F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields >25%, not decay corrected). The availability of ¹⁸F-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 ¹⁸F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional¹⁸F-FDG imaging.