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Development of 6‐[ 18 F]fluoro‐carbohydrate‐based prosthetic groups and their conjugation to peptides via click chemistry
Author(s) -
Collet Charlotte,
Maskali Fatiha,
Clément Alexandra,
Chrétien Françoise,
Poussier Sylvain,
Karcher Gilles,
Marie PierreYves,
Chapleur Yves,
LamandéLangle Sandrine
Publication year - 2016
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3362
Subject(s) - chemistry , glycopeptide , click chemistry , peptide , alkyne , moiety , dipeptide , positron emission tomography , combinatorial chemistry , carbohydrate , in vivo , radiochemistry , stereochemistry , organic chemistry , biochemistry , nuclear medicine , catalysis , medicine , microbiology and biotechnology , antibiotics , biology
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.