Open AccessEfficient 18 F‐Labeling of Synthetic Exendin‐4 Analogues for Imaging Beta Cells
Author(s) -
Keliher Edmund J.,
Reiner Thomas,
Thurber Greg M.,
Upadhyay Rabi,
Weissleder Ralph
Publication year - 2012
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201200014
Subject(s) - in vivo , chemistry , imaging agent , peptide , tetrazine , beta (programming language) , cysteine , conjugated system , combinatorial chemistry , biophysics , biochemistry , biology , enzyme , microbiology and biotechnology , organic chemistry , computer science , programming language , polymer
A number of exendin derivatives have been developed to target glucagon‐like peptide 1 (GLP‐1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin‐4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with 18 F‐ trans ‐cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging.