RT Journal Article SR Electronic T1 Development of 111In-labeled Exendin-4 derivative for the imaging of glucagon-like peptide-1 receptor expression in pancreatic islets JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1242 OP 1242 VO 55 IS supplement 1 A1 Kimura, Hiroyuki A1 Kambe, Kaori A1 Matsuda, Hirokazu A1 Toyoda, Kentaro A1 Fujimoto, Hiroyuki A1 Ono, Masahiro A1 Inagaki, Nobuya A1 Saji, Hideo YR 2014 UL http://jnm.snmjournals.org/content/55/supplement_1/1242.abstract AB 1242 Objectives The pancreatic β-cell mass is known to decrease as diabetes progresses. Thus, if a decrease in the amount of pancreatic β-cells can be detected at an early stage, there is a possibility of the prevention and treatment for diabetes. High densities of glucagon-like peptide-1 receptor (GLP-1R) expression in pancreatic β-cells provide an attractive target for imaging. Exendin-4 (Ex4), a peptide analog of GLP-1, can bind with high affinity to GLP-1R and is more stable than GLP-1 in vivo. In this study, we developed 111In-labeled Exendin-4 (111In-DTPA12-Ex4) targeting GLP-1R, and evaluated its utility as a SPECT probe for imaging of pancreatic GLP-1R. Methods The binding affinity of In-DTPA12-Ex4 to human GLP-1R was evaluated by competitive binding assay using the prepared membranes. The in vitro stability was characterized in mouse plasma. Biodistribution studies were carried out in normal ddY mice and STZ-treated diabetic mice. SPECT imaging was performed after injection of 111In-DTPA12-Ex4 into ddY mice. Results In-DTPA12-Ex4 had high affinity for GLP-1R (IC50 = 0.43 nM). 111In-DTPA12-Ex4 was stable in mouse plasma for 4 h. The in vivo biodistribution of 111In-DTPA12-Ex4 in ddy mice showed a high uptake in the pancreas (21.0 %ID/g at 1 hr) and high pancreas-to-blood (P/B = 41.7) and pancreas-to-liver (P/L = 14) ratios. The pancreas uptake of 111In-DTPA12-Ex4 in STZ-treated diabetic mice was decreased depending on fasting blood glucose level. Moreover, in SPECT images, pancreas was visualized by animal SPECT. Conclusions We demonstrated that 111In-DTPA12-Ex4 has a potential as an imaging probe detecting pancreatic GLP-1R.