Development of 99mTc-Labeled Pyridyl Benzofuran Derivatives To Detect Pancreatic Amylin in Islet Amyloid Model Mice

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• 作者：Masashi Yoshimura ; Masahiro Ono ; Hiroyuki Watanabe ; Hiroyuki Kimura ; Hideo Saji
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：June 15, 2016
• 年：2016
• 卷：27
• 期：6
• 页码：1532-1539
• 全文大小：394K
• 年卷期：0
• ISSN：1520-4812

文摘

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 two ^99mTc-labeled pyridyl benzofuran derivatives as novel amylin-imaging probes using the newly established islet amyloid model mouse. Binding experiments in vitro demonstrated that [^99mTc]1 displayed a higher affinity for amylin aggregates than [^99mTc]2. Autoradiographic studies using human pancreas sections with T2DM revealed that [^99mTc]1 clearly labeled islet amyloid in T2DM pancreatic sections, while [^99mTc]2 did not. Although the initial uptake of [^99mTc]1 by the normal mouse pancreas was low (0.74%ID/g at 2 min post-injection), [^99mTc]1 showed 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]1 is a potential imaging probe targeting islet amyloids in the T2DM pancreas.