IN VIVO DETECTION OF AMYLOID β DEPOSITION USING 19F MAGNETIC RESONANCE IMAGING WITH A 19F-CONTAINING CURCUMIN DERIVATIVE IN A MOUSE MODEL OF ALZHEIMER'S DISEASE
IN VIVO DETECTION OF AMYLOID β DEPOSITION USING 19F MAGNETIC RESONANCE IMAGING WITH A 19F-CONTAINING CURCUMIN DERIVATIVE IN A MOUSE MODEL OF ALZHEIMER'S DISEASE
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DOI：
10.1016/j.neuroscience.2011.03.071
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发表时间：
2011-06-16
期刊：
影响因子：
3.3
通讯作者：
Tooyama, I.
中科院分区：
文献类型：
--
作者：
Yanagisawa, D.;Amatsubo, T.;Tooyama, I.
淀粉样蛋白（A β）在大脑中的沉积被认为是阿尔茨海默病（AD）进展的起始事件。淀粉样蛋白成像在AD的诊断和疾病分期评价方面得到了广泛的研究，近年来取得了相当大的进展。我们已经开发了一种新的含有f -19的姜黄素衍生物（命名为FMeC1）作为潜在的显像剂。这种化合物可以在酮和烯醇互变异构体之间平衡存在，烯醇形式能够结合A β聚集体，而酮形式不能。本研究探讨FMeC1是否适合作为F-19磁共振成像（MRI）探针检测AD模型Tg2576小鼠a β沉积。在全头部F-19核磁共振（NMR）谱中，与野生型小鼠相比，外周注射FMeC1的Tg2576小鼠的F-19信号降低率延迟。此外，注射FMeC1后，F-19 MRI显示Tg2576小鼠脑内F-19信号水平显著。对注射fmec1的小鼠脑的组织学分析显示，在外周注射Tg2576小鼠中，该化合物穿过血脑屏障并与A β斑块结合。此外，Tg2576小鼠体内A β沉积的分布与F-19信号成像的大脑区域一致。FMeC1在人脑切片中也表现出对老年斑的亲和力。这些发现表明FMeC1作为一种F-19 MRI探针在检测脑内淀粉样蛋白沉积方面是有用的。此外，FMeC1的特性可以为进一步开发新型淀粉样蛋白成像探针奠定基础。(c) 2011 ibro。Elsevier Ltd.出版。版权所有。
Amyloid beta (A beta) deposition in the brain is considered the initiating event in the progression of Alzheimer's disease (AD). Amyloid imaging is widely studied in diagnosing AD and evaluating the disease stage, with considerable advances achieved in recent years. We have developed a novel F-19-containing curcumin derivative (named FMeC1) as a potential imaging agent. This compound can exist in equilibrium between keto and enol tautomers, with the enol form able to bind A beta aggregates while the keto form cannot. This study investigated whether FMeC1 is suitable as a F-19 magnetic resonance imaging (MRI) probe to detect A beta deposition in the Tg2576 mouse, a model of AD. In F-19 nuclear magnetic resonance (NMR) spectra obtained from the whole head, a delayed decreased rate of F-19 signal was observed in Tg2576 mice that were peripherally injected with FMeC1 in comparison to wild-type mice. Furthermore, F-19 MRI displayed remarkable levels of F-19 signal in the brain of Tg2576 mice after the injection of FMeC1. Histological analysis of FMeC1-injected mouse brain showed penetration of the compound across the blood brain barrier and binding to A beta plaques in peripherally injected Tg2576 mice. Moreover, the distribution of A beta deposits in Tg2576 mice was in accordance with the region of the brain in which the F-19 signal was imaged. FMeC1 also exhibited an affinity for senile plaques in human brain sections. These findings suggest the usefulness of FMeC1 as a F-19 MRI probe for the detection of amyloid deposition in the brain. Furthermore, the properties of FMeC1 could form the basis for further novel amyloid imaging probes. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.