A new technique for in vivo imaging of specific GLP-1 binding sites: first results in small rodents

Regul Pept. 2006 Dec 10;137(3):162-7. doi: 10.1016/j.regpep.2006.07.005. Epub 2006 Aug 22.

Abstract

Experimental objectives: In vivo imaging of GLP-1 receptor-positive tissues may allow examination of physiologic and pathophysiologic processes. Based on the GLP-1 analog Exendin 4, we have developed a radiolabeled compound specifically targeting the GLP-1 receptor (DTPA-Lys40-Exendin 4). This work aims to detect GLP-1 receptor-positive tissues by biodistribution studies and in vivo small animal imaging studies. For in vivo imaging, a high-resolution multi-pinhole SPECT (single photon emission computed tomography) system was used in conjunction with an MRI (magnetic resonance imaging) system for image fusion.

Results: DTPA-Lys40-Exendin 4 can be labeled with 111In to high specific activity (40 GBq/micromol). The radiochemical purity reliably exceeded 95%. Using this compound for in vivo small animal imaging of rats and mice as well as for biodistribution studies, specific GLP-1 binding sites could be detected in stomach, pancreas, lung, adrenals, and pituitary. Receptor-positive tissues were visualized with a high-resolution SPECT system with a resolution of less than 1 mm.

Conclusions: The new technique using DTPA-Lys40-Exendin 4 allows highly sensitive imaging of GLP-1 receptor-positive tissues in vivo. Therefore, intra-individual follow-up studies of GLP-1 receptor-positive tissue could be conducted in vivo.

MeSH terms

  • Animals
  • Binding Sites
  • Exenatide
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor
  • Image Processing, Computer-Assisted
  • Indium Radioisotopes
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Nude
  • Pentetic Acid
  • Peptides
  • Rats
  • Rats, Wistar
  • Receptors, Glucagon / metabolism
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Venoms

Substances

  • Glp1r protein, mouse
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Indium Radioisotopes
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • Pentetic Acid
  • Glucagon-Like Peptide 1
  • Exenatide