title: Development of 6-[(18) F]fluoro-carbohydrate-based prosthetic groups and their conjugation to peptides via click chemistry.
abstract: This work describes the development of new 6-[(18) F]fluoro-carbohydrate-based prosthetic groups equipped with an azido arm that are able to participate in copper(I)-catalyzed cycloadditions for (18) F labeling of biomolecules under mild conditions. The radiolabeling in high radiochemical yields (up to 68 ± 6%) of these different prosthetic groups is presented. The flexibility of the azido arm introduced on the carbohydrate moieties allows efficient click reactions with different alkyne functionalized peptides such as gluthation or Arg-Gly-Asp derivatives in order to prepare glycopeptides. The radiosyntheses of (18) F-labeled glycopeptides proceed in high radiochemical yields (up to 76%) in an automated process with excellent radiochemical purity. The addition of a sugar moiety on peptides should enhance the bioavailability, pharmacokinetic, and in vivo clearance properties of these glycopeptides, compared with the unlabeled native peptide, and these properties are highly favorable for positron emission tomography imaging. A high uptake of (18) F-β-gluco-c(RGDfC) is shown by positron emission tomography imaging in a subcutaneous abscess model in the rat, revealing the potential of this tracer to monitor integrin expression as a part of inflammation and/or angiogenesis processes.
authors.affiliation: Université de Lorraine, Vandoeuvre-les-Nancy, France.|Nancyclotep, Plateforme d'imagerie moléculaire, Vandoeuvre-les-Nancy, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Collet
authors.affiliation: Nancyclotep, Plateforme d'imagerie moléculaire, Vandoeuvre-les-Nancy, France.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Maskali
authors.affiliation: Nancyclotep, Plateforme d'imagerie moléculaire, Vandoeuvre-les-Nancy, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Clément
authors.affiliation: Université de Lorraine, Vandoeuvre-les-Nancy, France.|CNRS, UMR 7565, Vandoeuvre-les-Nancy, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Chrétien
authors.affiliation: Université de Lorraine, Vandoeuvre-les-Nancy, France.|Nancyclotep, Plateforme d'imagerie moléculaire, Vandoeuvre-les-Nancy, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Poussier
authors.affiliation: Université de Lorraine, Vandoeuvre-les-Nancy, France.|Nancyclotep, Plateforme d'imagerie moléculaire, Vandoeuvre-les-Nancy, France.|Département de Médecine Nucléaire, CHU-Nancy, Vandoeuvre les Nancy, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Karcher
authors.affiliation: Université de Lorraine, Vandoeuvre-les-Nancy, France.|Nancyclotep, Plateforme d'imagerie moléculaire, Vandoeuvre-les-Nancy, France.|Département de Médecine Nucléaire, CHU-Nancy, Vandoeuvre les Nancy, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Marie
authors.affiliation: Université de Lorraine, Vandoeuvre-les-Nancy, France.|Nancyclotep, Plateforme d'imagerie moléculaire, Vandoeuvre-les-Nancy, France.|CNRS, UMR 7565, Vandoeuvre-les-Nancy, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Chapleur
authors.affiliation: Université de Lorraine, Vandoeuvre-les-Nancy, France.|CNRS, UMR 7565, Vandoeuvre-les-Nancy, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lamandé-Langle
mesh_terms: D000818:Animals; D057930:Click Chemistry / Q000379:methods; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006020:Glycopeptides / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D006020:Glycopeptides; D019275:Radiopharmaceuticals
keywords: 18F; carbohydrate; click reaction; positron emission; prosthetic group; tomography