RT Journal Article
SR Electronic
T1 Development of in vivo imaging agents targeting glucagon-like peptide-1 receptor (GLP-1R) in pancreatic islets
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 326
OP 326
VO 50
IS supplement 2
A1 Kimura, Hiroyuki
A1 Ogawa, Yu
A1 Kawashima, Hidekazu
A1 Mukai, Eri
A1 Toyoda, Kentaro
A1 Fujimoto, Hiroyuki
A1 Hirao, Konomu
A1 Ono, Masahiro
A1 Inagaki, Nobuya
A1 Saji, Hideo
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/326.abstract
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.