PT  - JOURNAL ARTICLE
AU  - Kimura, Hiroyuki
AU  - Ogawa, Yu
AU  - Kawashima, Hidekazu
AU  - Mukai, Eri
AU  - Toyoda, Kentaro
AU  - Fujimoto, Hiroyuki
AU  - Hirao, Konomu
AU  - Ono, Masahiro
AU  - Inagaki, Nobuya
AU  - Saji, Hideo
TI  - Development of in vivo imaging agents targeting glucagon-like peptide-1 receptor (GLP-1R) in pancreatic islets
DP  - 2009 May 01
TA  - Journal of Nuclear Medicine
PG  - 326--326
VI  - 50
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/50/supplement_2/326.short
4100  - http://jnm.snmjournals.org/content/50/supplement_2/326.full
SO  - J Nucl Med2009 May 01; 50
AB  - 326 Objectives The beta cell mass is known to decrease as diabetes progresses. Developing a method to measure beta cell mass in vivo would be useful for the early diagnosis of diabetes. High densities of GLP-1R expression in pancreatic islets provide an attractive target for imaging. In this study, based on the GLP-1R antagonist exendin-(9-39) [ex(9-39)], we developed in vivo imaging agents specifically targeting GLP-1R. Methods N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) labeled [ex(9-39)] derivatives were synthesized and evaluated. To evaluate the distribution of [18F]FB-[ex(9-39)] derivatives in vivo, a biodistribution study was carried out in normal and GLP-1R KO mice. PET imaging studies were performed. Results The decay-corrected radiochemical yield of [18F]FB-[ex(9-39)] derivatives was about 7~18% and the radiochemical purity was greater than 99%. In vitro binding study indicated that the affinity of cold FB-[ex(9-39)] derivatives to GLP-1R was similar to ex(9-39). The in vivo biodistribution of [18F]FB12 and [18F]FB27-[ex(9-39)] in mice showed the high uptake in the pancreas (4.7% ID/g at 30 min and 4.1% ID/g at 15 min postinjection, respectively). A significant reduction of pancreas uptake was confirmed in GLP-IR KO mice. Moreover, we succeeded in visualizing the pancreas by PET. Conclusions For non-invasive imaging of pancreatic beta cells, ex(9-39) and GLP-1R can serve as a useful probe and target molecule, respectively.