Multiplex imaging of amyloid-β plaques dynamics in living brains with quinoline-malononitrile-based probes

IF 26.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Jianfeng Dai, Weijun Wei, Chenxu Yan, Ding-Kun Ji, Caiqi Liu, Jialiang Huang, Chenyi Liang, Jianjun Liu, Zhiqian Guo, Wei-Hong Zhu
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引用次数: 0

Abstract

The dynamic behaviour of amyloid-β (Aβ) plaques in Alzheimer’s disease remains poorly understood, and accumulation and distribution of Aβ plaques must be inferred from in vitro pathological changes in brain tissue. In situ detection of Aβ plaques in live imaging is challenging because of the lack of adequate probes. Here we report the design of unimolecular quinoline-malononitrile-based Aβ probes, termed QMFluor integrative framework, that binds in vivo to Aβ plaques, making them detectable via near-infrared fluorescence imaging, magnetic resonance imaging, positron emission tomography and computed tomography. QMFluor probes are permeable to the blood–brain barrier, and, upon systematic injection, enable real-time magnetic resonance imaging and positron emission tomography–computed tomography imaging of the Aβ biodistribution in the hippocampus and cerebral cortex, and accurately differentiate the brains of living Alzheimer’s disease mouse models from wild-type controls. We further demonstrate the ability of QMFluor probes to reach the brain after intravenous injection in a large animal model. This strategy expands the toolbox of probes for in vivo visualization of amyloids in Alzheimer’s disease pathological analysis, drug screening and clinical applications.

Abstract Image

基于喹啉-丙二腈探针的活体大脑淀粉样蛋白-β斑块动力学的多重成像
淀粉样蛋白-β (Aβ)斑块在阿尔茨海默病中的动态行为尚不清楚,β斑块的积累和分布必须从脑组织的体外病理变化中推断出来。由于缺乏足够的探针,在实时成像中原位检测Aβ斑块具有挑战性。在这里,我们报道了基于喹啉-丙二腈的单分子Aβ探针的设计,称为QMFluor整合框架,它与体内的Aβ斑块结合,使其通过近红外荧光成像,磁共振成像,正电子发射断层扫描和计算机断层扫描检测到。QMFluor探针可穿透血脑屏障,系统注射后,可实现海马和大脑皮层Aβ生物分布的实时磁共振成像和正电子发射断层扫描-计算机断层成像,并准确区分活体阿尔茨海默病小鼠模型和野生型对照组的大脑。我们在大型动物模型中进一步证明了QMFluor探针在静脉注射后到达大脑的能力。这一策略扩大了在阿尔茨海默病病理分析、药物筛选和临床应用中淀粉样蛋白体内可视化探针的工具箱。
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来源期刊
Nature Biomedical Engineering
Nature Biomedical Engineering Medicine-Medicine (miscellaneous)
CiteScore
45.30
自引率
1.10%
发文量
138
期刊介绍: Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.
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