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

• Published in: Regulatory peptides 2006-12, Vol.137 (3), p.162-167
• Main Authors: Gotthardt, Martin, Lalyko, Georg, van Eerd-Vismale, Julliëtte, Keil, Boris, Schurrat, Tino, Hower, Michael, Laverman, Peter, Behr, Thomas M., Boerman, Otto C, Göke, Burkhard, Béhé, Martin
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; Biological and medical sciences; Exendin 4; Fundamental and applied biological sciences. Psychology; GLP-1; Glucagon-Like Peptide 1 - metabolism; Glucagon-Like Peptide-1 Receptor; Image Processing, Computer-Assisted; Indium Radioisotopes; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Mice; Mice, Nude; Pentetic Acid; Peptides; Rats; Rats, Wistar; Receptor imaging; Receptors, Glucagon - metabolism; Single photon emission computed tomography; Small animal imaging; Tissue Distribution; Tomography, Emission-Computed, Single-Photon - methods; Venoms; Vertebrates: endocrinology
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2006.07.005

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-Lys 40-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. DTPA-Lys 40-Exendin 4 can be labeled with 111In to high specific activity (40 GBq/μmol). 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. The new technique using DTPA-Lys 40-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.