Development of 99mTc-labeled Pyridyl Benzofuran Derivatives to Detect Pancreatic Amylin in Islet Amyloid Model Mice.
Development of 99mTc-labeled Pyridyl Benzofuran Derivatives to Detect Pancreatic Amylin in Islet Amyloid Model Mice.
复制标题
开发 99mTc 标记的吡啶基苯并呋喃衍生物来检测胰岛淀粉样蛋白模型小鼠中的胰淀粉样蛋白。
DOI：
10.1021/acs.bioconjchem.6b00174
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发表时间：
2016
影响因子：
4.7
通讯作者：
Hideo Saji
中科院分区：
文献类型：
--
作者：
Masashi Yoshimura;Masahiro Ono;Hiroyuki Watanabe;Hiroyuki Kimura;Hideo Saji
胰岛淀粉样蛋白沉积是2型糖尿病（T2 DM）的病理标志之一，但目前尚无胰淀素成像探针的报道。在本研究中，我们评估了两个99 mTc标记的吡啶基苯并呋喃衍生物作为新的淀粉样蛋白成像探针使用新建立的胰岛淀粉样蛋白模型小鼠。体外结合实验表明，[99 mTc] 1对胰淀素聚集体的亲和力高于[99 mTc]2。应用人T2 DM胰腺切片的放射自显影研究显示，[99 mTc] 1在T2 DM胰腺切片中清楚地标记了胰岛淀粉样蛋白，而[99 mTc] 2则没有。虽然正常小鼠胰腺对[99 mTc] 1的初始摄取较低（注射后2 min为0.74%ID/g），但[99 mTc] 1在模型小鼠胰腺中的滞留率高于正常小鼠，并与模型小鼠活胰腺中的胰淀素聚集体表现出较强的结合。这些结果表明，[99 mTc] 1是一个潜在的成像探针靶向胰岛淀粉样蛋白在2型糖尿病胰腺。
While islet amyloid deposition comprising amylin is one of pathological hallmarks of type 2 diabetes mellitus (T2DM), no useful amylin-imaging probe has been reported. In this study, we evaluated two99mTc-labeled pyridyl benzofuran derivatives as novel amylin-imaging probes using the newly established islet amyloid model mouse. Binding experiments in vitro demonstrated that [99mTc]1displayed a higher affinity for amylin aggregates than [99mTc]2. Autoradiographic studies using human pancreas sections with T2DM revealed that [99mTc]1clearly labeled islet amyloid in T2DM pancreatic sections, while [99mTc]2did not. Although the initial uptake of [99mTc]1by the normal mouse pancreas was low (0.74%ID/g at 2 min post-injection), [99mTc]1showed higher retention in the model mouse pancreas than that of the normal mouse, and exhibited strong binding to amylin aggregates in the living pancreas of the model mice. These results suggest that [99mTc]1is a potential imaging probe targeting islet amyloids in the T2DM pancreas.