Development of 6-[(18) F]fluoro-carbohydrate-based prosthetic groups and their conjugation to peptides via click chemistry.
Fiche publication
Date publication
février 2016
Journal
Journal of labelled compounds & radiopharmaceuticals
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KARCHER Gilles, Pr MARIE Pierre-Yves
Tous les auteurs :
Collet C, Maskali F, Clément A, Chrétien F, Poussier S, Karcher G, Marie PY, Chapleur Y, Lamandé-Langle S
Lien Pubmed
Résumé
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.
Mots clés
Animals, Click Chemistry, methods, Fluorine Radioisotopes, chemistry, Glycopeptides, chemistry, Positron-Emission Tomography, Radiopharmaceuticals, chemical synthesis, Rats, Tissue Distribution
Référence
J Labelled Comp Radiopharm. 2016 Feb;59(2):54-62