Work

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

Year: 2015

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide We generated 18 F-labeled antibody fragments for positron emission tomography (PET) imaging using a sortase-mediated reaction to install a trans -cyclooctene-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled- 18 F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields > 25%, not decay corrected). The availability of 18 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 18 F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional 18 F-FDG imaging.

Source: ACS Central Science

DOI: 10.1021/acscentsci.5b00121

Authors: Mohammad Rashidian, Edmund J. Keliher, Michael Dougan, Patrick K. Juras, Marco Cavallari, Gregory R. Wojtkiewicz, Johanne T. Jacobsen, Jerre G. Edens, Jeroen M. J. Tas, Gabriel Victora, Ralph Weissleder, Hidde Ploegh

Institutions: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Massachusetts General Hospital, Center for Systems Biology, Harvard University

Language: English

Topic: Radiopharmaceutical Chemistry and Applications

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Lustgarten Foundation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Biomedical Imaging and Bioengineering

Awards: G1098359285, A new strategy to disrupt protein-protein interactions in eukaryotic cells., Novel Clickdyes for Biomedical Sensing, Non-invasive imaging of the immune response based on the use of isotopically labeled single domain antibody fragments, Center for Molecular Imaging Research at MGH/HMS, Sortase-mediated protein engineering for the study of host-pathogen interactions, G4882820107, G5230306093, Endosomal TLRs and their accessory proteins: cell biology and biochemistry, Genetics and Biology of Pancreatic Ductal Adenocarcinoma

OpenAlex ID: W2610778602

FWCI: 9.441

Cites: 38

Cited by: 98

Related to: 10