TY - JOUR T1 - Glucagon Like Peptide-1 receptor imaging in individuals with Type 2 Diabetes JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.121.262506 SP - jnumed.121.262506 AU - Olof Eriksson AU - Irina Velikyan AU - Torsten Haack AU - Martin Bossart AU - Iina Laitinen AU - Philip Just Larsen AU - Jan Erik Berglund AU - Gunnar Antoni AU - Lars Johansson AU - Stefan Pierrou AU - Joachim Tillner AU - Michael Wagner Y1 - 2021/09/01 UR - http://jnm.snmjournals.org/content/early/2021/09/09/jnumed.121.262506.abstract N2 - Introduction: The Glucagon Like 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. Positron Emission Tomography (PET) radioligand 68Ga-DO3A-VS-Exendin4 (68Ga-Exendin4) has the potential to enable longitudinal studies of the GLP1R in human pancreas. Methods: 68Ga-Exendin4 PET/CT examinations were acquired in overweight to obese individuals with type 2 diabetes (T2D) (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 <0.2µg/kg peptide, blood sampling and tracer stability assessment). Pancreas and abdominal organs were segmented and binding was correlated to clinical parameters. Results: The pancreatic uptake of 68Ga-Exendin4, but not in other abdominal tissues, was high but variable between individuals. There was no evidence of self-blocking of the GLP1R by the tracer in this protocol, despite the high potency of Exendin4. The results show that a full dynamic scan can be simplified to a short static scan, potentially increasing throughput and reduce patient discomfort. 68Ga-Exendin4 concentration in pancreas (i.e. GLP1R density) correlated inversely with the age of the individual, and had a tendency to correlate positively to BMI. However, the total GLP1R content in pancreas did not. Conclusion: In summary, we present an optimized and simplified 68Ga-Exendin4 scanning protocol, to enable reproducible imaging of the GLP1R in pancreas. 68Ga-Exendin4 PET may enable quantification of longitudinal changes of pancreatic GLP1R during the development in T2D, as well as target engagement studies of novel GLP-1 agonists. ER -