Glucagonlike Peptide-1 Receptor Imaging in Individuals with Type 2 Diabetes

• The glucagonlike peptide-1 receptor (GLP1R) is a gut hormone receptor, intricately linked to regulation of blood glucose homeostasis via several mechanisms. It is an established and emergent drug target in metabolic disease. The PET radioligand 68Ga-DO3A-VS-exendin4 (68Ga-exendin4) has the potential to enable longitudinal studies of GLP1R in the human pancreas.Methods: 68Ga-exendin4 PET/CT examinations were performed on overweight-to-obese individuals with type 2 diabetes (n = 13) as part of a larger target engagement study (NCT03350191). A scanning protocol was developed to optimize reproducibility (target amount of 0.5 MBq/kg [corresponding to peptide amount of <0.2 µg/kg], blood sampling, and tracer stability assessment). The pancreas and abdominal organs were segmented, and binding was correlated with clinical parameters.Results: Uptake of 68Ga-exendin4 in the pancreas, but not in other abdominal tissues, was high but variable between individuals. There was no evidence of self-blocking of GLP1R by the tracer in this protocol, despite the high potency of exendin4. The results showed that a full dynamic scan can be simplified to a short static scan, potentially increasing throughput and reducing patient discomfort. The 68Ga-exendin4 concentration in the pancreas (i.e., GLP1R density) correlated inversely with the age of the individual and tended to correlate positively with body mass index. However, the total GLP1R content in the pancreas did not.Conclusion: In summary, we present an optimized and simplified 68Ga-exendin4 scanning protocol to enable reproducible imaging of GLP1R in the pancreas. 68Ga-exendin4 PET may enable quantification of longitudinal changes in pancreatic GLP1R during the development of type 2 diabetes, as well as target engagement studies of novel glucagonlike peptide-1 agonists.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

GLP1R

PET

exendin

type 2 diabetes

b-cell mass

Publication and Content Type

ref (subject category)

art (subject category)