RT Journal Article
SR Electronic
T1 Glucagon Like Peptide-1 receptor imaging in individuals with Type 2 Diabetes
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.121.262506
DO 10.2967/jnumed.121.262506
A1 Olof Eriksson
A1 Irina Velikyan
A1 Torsten Haack
A1 Martin Bossart
A1 Iina Laitinen
A1 Philip Just Larsen
A1 Jan Erik Berglund
A1 Gunnar Antoni
A1 Lars Johansson
A1 Stefan Pierrou
A1 Joachim Tillner
A1 Michael Wagner
YR 2021
UL http://jnm.snmjournals.org/content/early/2021/09/09/jnumed.121.262506.abstract
AB 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.