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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-06-2011 | Short Communication

Value of the radiolabelled GLP-1 receptor antagonist exendin(9–39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

Authors: Beatrice Waser, Jean Claude Reubi

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2011

Abstract

Purpose

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans.

Methods

Receptor autoradiography studies with ¹²⁵I-GLP-1(7–36)amide agonist or ¹²⁵I-Bolton-Hunter-exendin(9–39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7–36)amide or exendin(9–39).

Results

The antagonist ¹²⁵I-Bolton-Hunter-exendin(9–39) labels mouse pancreatic β-cells and mouse insulinomas, but it does not label human pancreatic β-cells and insulinomas. High affinity displacement (IC₅₀ approximately 2 nM) is observed in mouse β-cells and insulinomas with either the exendin(9–39) antagonist or GLP-1(7–36)amide agonist. For comparison, the agonist ¹²⁵I-GLP-1(7–36)amide intensively labels mouse pancreatic β-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7–36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9–39) in the mouse and human tissues, respectively.

Conclusion

This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9–39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7–36)amide.

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Title: Value of the radiolabelled GLP-1 receptor antagonist exendin(9–39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans
Authors: Beatrice Waser
Jean Claude Reubi
Publication date: 01-06-2011
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-010-1701-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Value of the radiolabelled GLP-1 receptor antagonist exendin(9–39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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