Pancreatic β cell imaging using 64Cu- or 68Ga-labeled Exendin-4

合成了64Cu或68Ga标记的Exendin-4，并进行了正电子发射计算机断层扫描。采用硫代酯法合成DOTA-Exendin-4。将含有DOTA部分的N-末端片段[DOTA-Exendin(1-4)]与C-末端片段[Exendin-4(5-39)]缩合得到DOTA-Exendin4。得到的DOTA-Exendin-4可以用Ga-68标记。利用铜结合基序(ATCUN)合成了64铜标记的Exendin-4。带有ATCUN基序的Exendin-4可以用铜-标记。进行了宠物成像和生物分布研究。生物分布研究表明，在肝脏和胰腺中有较高的蓄积量。PET显像结果显示，注射后30min内可观察到胰腺的蓄积。30min以上，代谢的探针被分泌到胆汁中。因此，胰腺的蓄积不能与包括胆汁在内的肠道区分开来。

64Cu- or 68Ga-labeled Exendin-4 was synthesized and PET imagings were performed. DOTA-Exendin-4 was synthesized by thioester method. N-terminal segment with DOTA moiety [DOTA-Exendin(1-4)] was condensed with C-terminal segment [Exendin-4(5-39)] to give DOTA-Exendin4. Obtained DOTA-Exendin-4 could be labeled with Ga-68. 64Cu-labeled Exendin-4 was synthesized utilizing Cu binding motif (ATCUN). Exendin-4 with ATCUN motif was could be labeled with Cu-64. PET imagings and biodistribution studies were performed. Biodistribution studies revealed the high accumulation in liver and pancreas. The results of PET imaging, the accumulation of pancreas was determined within 30min after injection. Over 30min, metabolized probe was secreted into the bile. So the accumulation of pancreas could not be distinguished from the intestine including the bile.