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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-06-2014 | Original Article

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

Authors: Beatrice Waser, Jean Claude Reubi

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2014

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Title: Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues
Authors: Beatrice Waser
Jean Claude Reubi
Publication date: 01-06-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-013-2684-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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