Association of Glucagon-like Peptide-1 Receptor (GLP-1R)-targeted Imaging Probe with In-vivo GLP-1R Agonist Glucose-lowering Effects.

AIMS AND INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients don't respond well to the therapy and cautions must be taken for certain patients including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP-1RA therapy. To visualize and quantify beta-cells, GLP-1R-targeted imaging has emerged recently. We investigated whether GLP-1R-targeted imaging can predict the efficacy of GLP-1RA treatment. MATERIALS AND METHOD: We developed 111Indium-labeled exendin-4 derivative (111In-Ex4) as a GLP-1R-targeting probe. Diabetic mice were selected from NONcNZO10/LtJ male mice that were fed for different durations with 11%-fat chow. After 3-week administration of dulaglutide as GLP-1RA therapy, mice with non-fasting blood glucose levels under and over 300 mg/dL were defined as responders and non-responders, respectively. In addition, ex-vivo 111In-Ex4 pancreatic accumulations (111In-Ex4 pancreatic values) were examined. RESULTS: The non-fasting blood glucose levels after treatment were 172.5+/-42.4 mg/dL in responders (n=4) and 330.8+/-20.7 mg/dL in non-responders (n=5), respectively. Ex-vivo (111) In-Ex4 pancreatic values showed significant correlations with post-treatment glycohemoglobin and glucose area under curve (AUC) during oral glucose tolerance test (R2=0.76 and 0.80; p<0.01 and <0.01, respectively). The receiver operating characteristic AUC for identifying responders by ex-vivo (111) In-Ex4 pancreatic values was 1.00 (p<0.01). CONCLUSION: Ex-vivo (111) In-Ex4 pancreatic values reflected dulaglutide efficacy, suggesting clinical possibilities for expanding GLP-1R-targeted imaging applications.