Introduction: Glucagon-like peptide-1 (GLP-1) and its analogues have important roles in several pathways associated with obesity and related diseases. For example, GLP-1 induces satiety and results of bariatric surgery can partly be explained by increased GLP-1 levels. However, localization of its receptor (GLP-1R) is not completely understood in humans and has never been studied in vivo. Radiolabeled exendin-4 has been developed to target beta cells via GLP-1R. In this study we aimed to determine whole body distribution of this radiotracer in participants of ongoing studies. 

Methods: 62 participants were included from ongoing studies into insulinoma detection, type 1 diabetes, obesity and type 2 diabetes (T2D) and post-bariatric outcomes. All participants received 75-100 MBq ⁶⁸Ga-exendin-4 (4-7 µg peptide) and underwent PET/CT one hour after administration. Abdominal imaging was performed in all participants (n=62) and chest, head and pelvic imaging in respectively 57, 41 and 8 participants. Radiotracer distribution was assessed visually and quantitatively.

Results: Clear radiotracer uptake was observed in the pancreas and duodenum in all participants. The majority of participants showed uptake in salivary glands (95%) and pituitary gland (78%). Other structures in the brain did not show any uptake. Additionally, uptake in cardiac tissue was observed in four participants (7%). Of the female participants, half had uptake in glandular breast tissue (47%) and uterus and ovary (4 out of 8).

Conclusion: We demonstrated uptake of ⁶⁸Ga-exendin-4 in several extrapancreatic locations, which mostly match with known GLP-1R expression. Except from the pituitary, no uptake was observed in the brain, although GLP-1R expression is known in, e.g. hypothalamic nuclei. These findings suggest that exendin-4 PET is a very promising tool to visualize GLP-1R expression in vivo and a valuable tool for studying obesity and related diseases, and treatment responses of GLP-1 analogues.