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

Eur J Nucl Med Mol Imaging. 2014 Jun;41(6):1166-71. doi: 10.1007/s00259-013-2684-4. Epub 2014 Feb 12.


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 (125)iodinated-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 (125)I-GLP-1(7-36)amide.

Methods: Receptor autoradiography studies with (125)I-GLP-1(7-36)amide agonist or (125)I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues.

Results: The antagonist (125)I-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 (125)I-GLP-1(7-36)amide. For comparison, (125)I-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 (125)I-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.

MeSH terms

  • Animals
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Neoplasms / diagnostic imaging
  • Peptide Fragments / pharmacokinetics*
  • Protein Binding
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Receptors, Glucagon / agonists
  • Receptors, Glucagon / antagonists & inhibitors*
  • Receptors, Glucagon / metabolism
  • Succinimides / pharmacokinetics*
  • Tissue Distribution


  • 125I-Bolton-Hunter-exendin(9-39)
  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Radiopharmaceuticals
  • Receptors, Glucagon
  • Succinimides
  • exendin (9-39)
  • Bolton-Hunter reagent