A new technique for in vivo imaging of specific GLP-1 binding sites: first results in small rodents.
OBJECTIVE
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.
Gotthardt
Martin
M
Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Postbus 9101, 6500 HB Nijmegen, The Netherlands. m.gotthardt@nucmed.umcn.nl
Lalyko
Georg
G
van Eerd-Vismale
Julliëtte
J
Keil
Boris
B
Schurrat
Tino
T
Hower
Michael
M
Laverman
Peter
P
Behr
Thomas M
TM
Boerman
Otto C
OC
Göke
Burkhard
B
Béhé
Martin
M
D000818:Animals; D001665:Binding Sites; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D007091:Image Processing, Computer-Assisted; D007205:Indium Radioisotopes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D004369:Pentetic Acid; D010455:Peptides; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014688:Venoms
C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007205:Indium Radioisotopes; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D004369:Pentetic Acid; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide