突触囊泡蛋白2A显像剂^(18)F-SynVesT-1在阿尔茨海默病患者中的应用  

Chinical application of synaptic vesicle protein 2A radioactive tracer^(18)F-SynVesT-1 in patients with Alzheimer′s disease

作　　者：何坤 李骏鹏 沙海 钱玥 王杰 黄琪 赵军[2] 郭起浩 管一晖[1] 谢芳[1] He Kun;Li Junpeng;Sha Hai;Qian Yue;Wang Jie;Huang Qi;Zhao Jun;Guo Qihao;Guan Yihui;Xie Fang(Department of Nuclear Medicine&PET Center,Huashan Hospital,Fudan University,Shanghai,200235;Department of Nuclear Medicine,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,200120;Department of Gerontology,Shanghai Jiao Tong University Affiliated Sixth People′s Hospital,Shanghai,200233)

机构地区：[1]复旦大学附属华山医院核医学/PET中心,上海200235 [2]同济大学附属东方医院核医学科,上海200120 [3]上海交通大学附属第六人民医院老年病科,上海200233

出　　处：《中华核医学与分子影像杂志》2024年第5期291-296,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：科技创新2030-"脑科学与类脑研究"重大项目(2022ZD0213800);国家自然科学基金(82071962)。

摘　　要：目的探讨突触囊泡蛋白2A显像剂(4R)-4-(3-[^(18)F]氟苯基-5-氟)-1-[(3-甲基吡啶-4-基)甲基]吡咯烷-2-酮(^(18)F-SynVesT-1)在阿尔茨海默病(AD)患者中的应用价值。方法回顾性纳入2021年12月至2022年12月间于复旦大学附属华山医院行^(18)F-SynVesT-1 PET/MR和^(18)F-氟贝他吡(AV45)PET/CT显像的受检者40例,包括20例β-淀粉样蛋白(Aβ)沉积阳性的AD患者[男2例,女18例;年龄(66.4±8.1)岁]和20名Aβ沉积阴性的正常对照[NC;男9例,女11例,年龄(62.6±8.6)岁]。利用统计参数图(SPM)对脑^(18)F-SynVesT-1 PET图像进行预处理。采用两独立样本t检验或Mann-Whitney U检验进行基于ROI的2组间^(18)F-SynVesT-1摄取(突触密度)差异比较,并进行突触密度与认知能力的Spearman秩相关分析。通过构建广义线性模型,采用两样本独立t检验分析2组脑内突触密度差异,进一步构建多重线性回归模型分析^(18)F-SynVesT-1与认知能力的相关性。结果AD患者组相比于NC组,其大脑广泛皮质区域突触密度减低[P<0.05,错误发现率(FDR)校正],其中以内侧颞叶(0.84±0.09和1.04±0.09;t=-6.95,P<0.001)、外侧颞叶(1.15±0.13和1.31±0.08;t=-4.56,P<0.001)和外侧顶叶[1.24(1.04,1.26)和1.32(1.23,1.39);z=-3.25,P=0.001]较为显著;大脑广泛皮质区域的突触密度与简易精神状态检查量表(MMSE)和蒙特利尔认知评估基础量表(MoCA-B)评分呈正相关(P<0.05,FDR校正),其中MMSE和MoCA-B评分与外侧颞叶(rs值:0.71、0.74,均P<0.001)和内侧颞叶(rs值:0.71、0.74,均P<0.001)突触密度存在明显相关性。结论^(18)F-SynVesT-1 PET显像可用于评估大脑突触密度;AD患者脑内表现为大脑广泛皮质区域的突触密度降低,且可反映患者认知水平。Objective To investigate the application of(4R)-4-(3-[^(18)F]fluoranyl-5-fluorophenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one(^(18)F-SynVesT-1),a synaptic vesicle glycoprotein 2A(SV2A)radioactive tracer,in patients with Alzheimer′s disease(AD).Methods A total of 20 AD patients(2 males,18 females,age(66.4±8.1)years)with positiveβ-amyloid(Aβ)deposition and 20 normal controls(NC;9 males,11 females,age(62.6±8.6)years)without Aβdeposition were retrospectively recruited from Huashan Hospital,Fudan University between December 2021 and December 2022.All of them underwent^(18)F-SynVesT-1 PET/MR and^(18)F-Florbetapir(AV45)PET/CT scans.Preprocessing of brain^(18)F-SynVesT-1 PET images was carried out using statistical parametric mapping(SPM).The differences of the uptke of^(18)F-SynVesT-1(synaptic density)between two groups based on ROI were compared by using either the independent-sample t test or Mann-Whitney U test.Spearman rank correlation analysis was performed to assess the relationship between synaptic density and cognitive performance.For voxelwise analysis,a general linear model was constructed to analyze differences in synaptic density between the two groups using the independent-sample t test.Furthermore,a multiple linear regression model was developed to explore the relationship between synaptic density and cognitive performance.Results Compared to the NC group,the AD group exhibited significant widespread reduction in synaptic density across the cortical regions(P<0.05,false discovery rate(FDR)-corrected),particularly in the medial temporal lobe(0.84±0.09 vs 1.04±0.09;t=-6.95,P<0.001),lateral temporal lobe(1.15±0.13 vs 1.31±0.08;t=-4.56,P<0.001),and lateral parietal lobe(1.24(1.04,1.26)vs 1.32(1.23,1.39);z=-3.25,P=0.001).Moreover,synaptic density in extensive cortical regions showed a positive correlation with mini-mental state examination(MMSE)and Montreal cognitive assessment-basic(MoCA-B)scores(P<0.05,FDR-corrected).Notably,significant associations were observed between MMSE and MoCA-B s

关 键 词：阿尔茨海默病 淀粉样β肽类 膜糖蛋白类 吡咯烷类 正电子发射断层显像术 磁共振成像 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R816.1[医药卫生—临床医学]