脑淀粉样血管病(CAA)是一种与β-淀粉样蛋白(Aβ)有关的脑血管病变，它严重威胁老年人身心健康，它的早期确诊有助于多种相关疾病的防治，而目前CAA诊断药物研究较少，效果一般，因此优良CAA显像剂的研发势在必行。本项目以脑血管壁沉积的Aβ蛋白为靶点，在前期研究基础上对刚性共轭平面的苯基苯并噻唑类衍生物和新型柔性Aβ探针结构进行修饰，通过体内外多种方法对探针的稳定性、脂溶性、亲和力、特异性、脑摄取与清除能力等多方面进行评价，以期筛选出与CAA患者脑血管壁Aβ具有高亲和性和选择性的PET显像剂，为实现CAA的早期无创伤准确诊断奠定理论与实践基础。此外，刚性平面结构的苯基苯并噻唑类衍生物采用新型的Al18F水溶液标记方法以及柔性分子探针与Aβ蛋白结合模式的探索也是本项目的研究重点。本项目对推动具有我国自主知识产权的新型放射性药物研发具有重要意义。

Cerebral amyloid angiopathy (CAA), one type of cerebrovascular diseases is related to β-amyloid protein (Aβ). It brings a serious threat to the physical and mental health of the elderly. An early accurate diagnosis of CAA is beneficial to the prevention and treatment of various related disease. However, the current research on imaging agents for CAA is limited and the effect is moderate. Therefore, the study of excellent CAA imaging agents is imperative. The rigid planar scaffold and novel flexible structure are two types of Aβ probes. In this project, we will design and synthesize Al18F-labeled phenylbenzothiazole derivatives and 18F-labeled novel flexible ligands targeting Aβ deposition in blood vessel walls of the brain, and then evaluate their properties including stability, lipophilicity, affinity, specificity, the ability of BBB penetration and washout by various methods. The aim of this project is to screen out novel PET probes with high binding affinity and selectivity to Aβ deposition in blood vessels of CAA patient, and lay the theoretical and practical basis for the early definitive detection of CAA by PET imaging. In addition, the novel labelling method of Al18F in aqueous solution for the rigid planar scaffold (phenylbenzothiazole derivatives) and new binding modes between the flexible probes and Aβ protein will be explored in this project. The research is of great significance for promoting the development of novel radiopharmaceuticals with independent intellectual property right for our country.