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Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
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Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas

Maarten Brom1, Lieke Joosten, Wim J G Oyen

  • 1Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500, HB Nijmegen, The Netherlands. m.brom@nucmed.umcn.nl

Contrast Media & Molecular Imaging
|March 22, 2012
PubMed

Insights

Glucagon-like peptide-1 receptor (GLP-1R) agonists exendin-3 and exendin-4 show promise for in vivo tumor targeting. The GLP-1R antagonist exendin(9-39) demonstrated poor tumor uptake and is unsuitable for this application.

Area of Science:

  • Radiopharmaceutical chemistry
  • Molecular imaging
  • Endocrinology

Background:

  • Internalizing agonists are typically used for peptide receptor targeting.
  • Non-internalizing receptor antagonists are emerging as potential alternatives for targeted therapies.
  • The glucagon-like peptide-1 receptor (GLP-1R) is a target for various therapeutic applications.

Purpose of the Study:

  • To evaluate the potential of the GLP-1R antagonist exendin(9-39) for in vivo targeting of GLP-1R expressing tumors.
  • To compare the in vitro and in vivo characteristics of exendin(9-39) with the GLP-1R agonists exendin-3 and exendin-4 for tumor targeting.

Main Methods:

  • In vitro determination of binding and internalization kinetics of labeled exendin-3, exendin-4, and exendin(9-39) using INS-1 cells.
  • In vivo evaluation of the targeting properties of radiolabeled exendin-3, exendin-4, and exendin(9-39) in mice bearing subcutaneous INS-1 tumors.

Main Results:

  • All labeled exendins exhibited similar in vitro binding affinities (IC50 values).
  • Exendin-3 and exendin-4 demonstrated rapid in vitro binding and internalization, while exendin(9-39) showed lower binding and minimal internalization.
  • In vivo studies revealed high specific tumor uptake for exendin-3 and exendin-4, whereas exendin(9-39) showed significantly low and transient tumor uptake.

Conclusions:

  • GLP-1R agonists, exendin-3 and exendin-4, labeled with Indium-111, are suitable for in vivo GLP-1R targeting in tumors.
  • The GLP-1R antagonist exendin(9-39) is not effective for in vivo GLP-1R tumor targeting due to poor uptake and rapid clearance.

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