PT  - JOURNAL ARTICLE
AU  - Kimura, Hiroyuki
AU  - Kambe, Kaori
AU  - Matsuda, Hirokazu
AU  - Toyoda, Kentaro
AU  - Fujimoto, Hiroyuki
AU  - Ono, Masahiro
AU  - Inagaki, Nobuya
AU  - Saji, Hideo
TI  - Development of <sup>111</sup>In-labeled Exendin-4 derivative for the imaging of glucagon-like peptide-1 receptor expression in pancreatic islets
DP  - 2014 May 01
TA  - Journal of Nuclear Medicine
PG  - 1242--1242
VI  - 55
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/55/supplement_1/1242.short
4100  - http://jnm.snmjournals.org/content/55/supplement_1/1242.full
SO  - J Nucl Med2014 May 01; 55
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.