title: Imaging sialylated tumor cell glycans in vivo.
abstract: Cell surface glycans are involved in numerous physiological processes that involve cell-cell interactions and migration, including lymphocyte trafficking and cancer metastasis. We have used a bioorthogonal metabolic labeling strategy to detect cell surface glycans and demonstrate, for the first time, fluorescence and radionuclide imaging of sialylated glycans in a murine tumor model in vivo. Peracetylated azido-labeled N-acetyl-mannosamine, injected intraperitoneally, was used as the metabolic precursor for the biosynthesis of 5-azidoneuraminic, or azidosialic acid. Azidosialic acid-labeled cell surface glycans were then reacted, by Staudinger ligation, with a biotinylated phosphine injected intraperitoneally, and the biotin was detected by subsequent intravenous injection of a fluorescent or radiolabeled avidin derivative. At 24 h after administration of NeutrAvidin, labeled with either a far-red fluorophore or (111)In, there was a significant azido-labeled N-acetyl-mannosamine-dependent increase in tumor-to-tissue contrast, which was detected using optical imaging or single-photon-emission computed tomography (SPECT), respectively. The technique has the potential to translate to the clinic, where, given the prognostic relevance of altered sialic acid expression in cancer, it could be used to monitor disease progression.
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: André A
authors.initials: AA
authors.lastname: Neves
authors.forename: Henning
authors.initials: H
authors.lastname: Stöckmann
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Harmston
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Pryor
authors.forename: Israt S
authors.initials: IS
authors.lastname: Alam
authors.forename: Heather
authors.initials: H
authors.lastname: Ireland-Zecchini
authors.forename: David Y
authors.initials: DY
authors.lastname: Lewis
authors.forename: Scott K
authors.initials: SK
authors.lastname: Lyons
authors.forename: Finian J
authors.initials: FJ
authors.lastname: Leeper
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D012794:Sialic Acids / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D011134:Polysaccharides; D012794:Sialic Acids