用于阿尔茨海默症早期诊断的氟标小分子MRI成像用Aβ探针的研究

项目名称： 用于阿尔茨海默症早期诊断的氟标小分子MRI成像用Aβ探针的研究

项目编号： No.81501187

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 乔金平

作者单位： 安徽医科大学

项目金额： 17.5万元

中文摘要： 阿茨海默症（AD）以神经退行性病变和认知障碍为主要特征，严重危害老年人健康。目前，认知和神经病理检查均难以早期诊断AD。随着氟18-AV45等获FDA批准，PET用Aβ探针的显像已实现AD的早期诊断。MRI较PET更安全经济，氟19小分子探针在MRI脑显像中有突出优势。但现有氟19Aβ探针如FSB等,在动物MRI成像中均未显示出AD早期病理性特异的散在分布的Aβ斑块。原因可能是现有氟标探针的氟原子数较少，且分子量过大。本课题拟采用多氟标记策略，既保持探针的小分子量，又标记上多个氟原子。申请人前期筛选的茚酮衍生物能特异结合Aβ斑块，拥有良好的亲和力和脑摄取量，有诱人的应用前景。本研究拟用氟19的放射性同位素氟18标记，利用受体结合、放射自显影等技术，快速准确地筛选评价待测探针。预期将能实现对散在分布的Aβ斑块进行准确清晰的MRI成像，为AD 的MRI早期诊断提供新技术。本研究国内外未见报道。

中文关键词： Aβ探针；AD早期诊断；氟标分子探针；分子影像探针；磁共振成像

英文摘要： Alzheimer's disease (AD) which is characterized by neurodegeneration and cognitive impairment serious harm to the health of the elderly. Currently, cognitive and neuropathological examination is difficult to early diagnose AD. With the approve of fluorine 18-AV45 by FDA, PET imaging of Aβ probes has been achieved early diagnosis of AD. MRI is more secure and cheap than PET. Fluorine 19 (19F) labeled small molecular probes have outstanding advantages in MRI brain imaging. Scatter distributed Aβ plaques are pathological specific in the early stage of AD brain. However, they could not be detected by FSB and other existing MRI 19F Aβ probes animal MRI imaging, probably due to insufficient amount of 19F atoms and an oversize molecular weight in the existing probes. This study intends to use more fluorine atoms labeling strategies. The probe will be labeled more amount of 19F atoms while keeping a smaller molecular weight. Previous work of the applicant showed that the indanone derivatives were able to bind to the Aβ plaques specifically and with fine affinity and brain uptake. The derivatives had an attractive prospect. In this study, the 18F which is a radioactivity isotope of 19F will be labeled to the probe. Then the related techniques such as the receptor binding assay, autoradiography and so on will be used to screen and evaluate the 19F labeled probes quickly and accurately. It is expected to get the probe which could image the scatter distributed Aβ plaques accurately and clearly. And it will provide new techniques for early diagnosis of AD by MRI molecular imaging test. This study was not found to be reported at home and abroad.

英文关键词： Aβ probe;AD early diagnosis;fluorine labeled molecular probe;Molecular imaging probe;MRI