项目名称: 用于AD早期诊断的近红外Aβ斑块荧光分子探针及对应放射性核素标记探针的研究
项目编号: No.21201019
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 无机化学
项目作者: 崔孟超
作者单位: 北京师范大学
项目金额: 25万元
中文摘要: 阿尔茨海默症(Alzheimer's Disease,AD)是老年痴呆的一种最常见形式,已成为继肿瘤、心脏病和中风之后,严重威胁老年人身心健康的主要疾病之一,而AD只能通过病人死后尸检脑内的Aβ斑块来确诊。目前,我国正在快速步入老龄化社会,AD的防治工作任务艰巨,研究AD的早期诊断方法具有极其重要的意义。因此,本课题将以脑内Aβ斑块为靶点,设计并制备一系列具有推-拉电子结构的近红外荧光探针,通过荧光染色实验、体外竞争结合实验、正常小鼠体内分布实验、AD转基因小鼠活体荧光显像实验等多种方法对它们进行全面的生物学评价,筛选出与Aβ斑块具有高亲和性和选择性的近红外Aβ斑块荧光分子探针,通过光学成像的方法实现早期、无创伤的准确诊断AD。同时,这些荧光探针可以方便地进行11C或18F标记,开发成用于PET显像的Aβ斑块显像剂。
中文关键词: 阿尔茨海默症;Aβ斑块;近红外;分子探针;
英文摘要: Alzheimer's disease (AD) is the most common form of dementia characterized by symptoms such as progressive loss of memory and other cognitive functions. However, the clinical diagnosis of this disease is often difficult and unreliable. A definitive diagnosis of AD can only be established by demonstrating the presence of abundant Aβ plaques in the postmortem brain. Currently,our country is stepping into the aging society rapidly.There is an arduous task for the prevention and treatment of AD, thus the early detection of AD is more important than ever. In this project, we will design and synthesis a novel series of near-infrared imaging probes with push-pull moiety, and evaluate these probes by in vitro fluorescent staining, in vitro binding assays using Aβ(1-42) aggregates, in vivo biodistribution in normal mice and in vivo optical imaging using APP/PS1 transgenic mice.The aim of this project is to screen out novel near-infrared probes with high binding affinity and selectivity to Aβ plaques, and apply them to the early and non-invasive diagnosis of AD using optical imaging method. In addition, these near-infrared probes can be easily labeled by 11C or 18F, and be develop to positron emission tomography (PET) tracers for Aβ plaques.
英文关键词: Alzheimer's disease;Aβ plaque;near-infrared;imaging probe;