title: The use of18F-2-fluorodeoxyglucose (FDG) to label antibody fragments for immuno-PET of pancreatic cancer.
abstract: We generated18F-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 of18F-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 to18F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional18F-FDG imaging.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rashidian
authors.affiliation: Center for Systems Biology Department, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114 (USA).
authors.forename: Edmund
authors.initials: E
authors.lastname: Keliher
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Gastroenterology, Massachusetts General Hospital Boston, 185 Cambridge St., MA 02114.
authors.forename: Michael
authors.initials: M
authors.lastname: Dougan
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Juras
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Marco
authors.initials: M
authors.lastname: Cavallari
authors.affiliation: Center for Systems Biology Department, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114 (USA).
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Wojtkiewicz
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Johanne
authors.initials: J
authors.lastname: Jacobsen
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Jerre G
authors.initials: JG
authors.lastname: Edens
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Jeroen M G
authors.initials: JM
authors.lastname: Tas
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Victora
authors.affiliation: Center for Systems Biology Department, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114 (USA); Department of Systems Biology, Harvard Medical School 200 Longwood Ave, Boston, MA 02115.
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Hidde
authors.initials: H
authors.lastname: Ploegh