Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues
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Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125iodinated-Bolton-Hunter (BH)-exendin(9–39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125I-GLP-1(7–36)amide.
Receptor autoradiography studies with 125I-GLP-1(7–36)amide agonist or 125I-BH-exendin(9–39) antagonist radioligands were performed in human and rat tissues.
The antagonist 125I-BH-exendin(9–39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125I-GLP-1(7–36)amide. For comparison, 125I-BH-exendin(9–39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues.
The GLP-1 receptor antagonist exendin(9–39) labelled with 125I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients.
KeywordsHuman tumours GLP-1 receptors Exendin(9–39) antagonist Tumour targeting Peptide receptors
We thank Drs. Werner Hassler and Ulrich Matthey, Zurich, Switzerland as well as Drs. Charles Pyke and Lotte Bjerre-Knudsen, Copenhagen, Denmark for helpful discussions.
Conflicts of interest
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