影像诊断阿尔茨海默病的PET显影剂研究进展  

Progress of PET imaging tracers for Alzheimer's disease diagnosis

作　　者：龙睿玲 王力 LONG Rui-ling;WANG Li(Department of Nuclear Medicine/Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province/Academician(Expert)Workstation of Sichuan Province,Affiliated Hospital of Southwest Medical University,Luzhou SICHUAN 646000,China;School of Pharmacy,Southwest Medical University,Luzhou SICHUAN 646000,China)

机构地区：[1]西南医科大学附属医院核医学科/核医学与分子影像四川省重点实验室/四川省院士(专家)工作站,四川泸州646000 [2]西南医科大学药学院,四川泸州646000

出　　处：《中国新药与临床杂志》2024年第7期494-503,共10页Chinese Journal of New Drugs and Clinical Remedies

基　　金：西南医科大学附属医院博士启动基金(20015)。

摘　　要：阿尔茨海默病(AD)是不可逆性痴呆症中最常见的形式。除了评估AD患者记忆能力,正电子发射断层扫描(PET)作为一种灵敏度较高的非侵入性诊断方式,还可以对靶点进行定性或定量的影像诊断,定性及定量评价β淀粉样蛋白(Aβ)、tau蛋白、突触蛋白等相关生物标志物,对AD诊断具有重要意义。硫代黄素-T衍生物[^(18)F]氟替莫尔和苯乙烯吡啶及二苯乙烯衍生物[^(18)F]氟倍他滨、[^(18)F]氟倍他平能与Aβ高度特异性地结合,作为PET显影剂被FDA批准上市。^(68)Ga、^(64)Cu标记的放射性显影剂同样表现出高度的Aβ斑块亲和力。喹啉衍生物[^(18)F]-THK5351和[^(18)F]-PPQ8、吡啶吲哚衍生物[^(18)F]-T807、兰索拉唑衍生物[^(11)C]-NML均可量化tau蛋白错误折叠导致的神经纤维缠结程度。左乙拉西坦结构衍生物[^(11)C]-UCB-J、[^(18)F]-SDM-8可以测量突触密度,3-氟-4-乙炔基苄腈衍生物[^(18)F]-FPEB则通过与代谢型谷氨酸受体第5亚型(m Glu R5)的结合用于AD的辅助诊断,酮色林类衍生物[^(18)F]-altanserin则通过作用于5-羟色胺用于研究早期AD的分子变化。Alzheimer's disease(AD)is the most common form of irreversible dementia.In addition to assessing of patients'memory abilities,positron emission tomography(PET),as a non-invasive diagnostic modality with high sensitivity and qualitative or quantitative imaging of the target sites,can qualitatively and quantitatively evaluateβ-amyloid(Aβ),tau proteins,synaptic proteins,and other related biomarkers,which is of great significance in the diagnosis of AD.As PET imaging approved by FDA,[^(18)F]-flutemetamol,a derivative of^(18)F labelled thioflavin-T,and[^(18)F]-florbetaben,[^(18)F]-florbetapir,which are phenylpyridine derivates,have high specificity in their affinity for Aβplaque binding.Other radionuclides such as^(68)Ga and^(64)Cu labeled radiotracers also showed high affinity with Aβplaques.Quinoline derivatives[^(18)F]-THK5351,[^(18)F]-PPQ8,benzimidazolopyrimidine and pyridine-indole derivatives[^(18)F]-T807,and lansoprazole derivatives[^(11)C]-NML as PET imaging agents,can quantify tau protein tangles.And the structural derivatives of levetiracetam[^(11)C]-UCB-J and[^(18)F]-SDM-8 can measure synaptic density,while the structural derivatives[^(18)F]-FPEB of 3-fluoro-4-acetylidene-benzylnitrile can assist in the diagnosis of AD by binding with m Glu R5.The fluorobenzoyl derivative[^(18)F]-altanserin,with ketoserin as its structural parent,acts on 5-hydroxytryptamine to study the molecular changes of early AD.

关 键 词：阿尔茨海默病 正电子发射断层扫描 淀粉样蛋白 TAU蛋白质类 放射性药物 

分 类 号：R981.9[医药卫生—药品]