摘要目的:探讨突触囊泡蛋白2A显像剂(4R)－4－(3－[ 18F]氟苯基－5－氟)－1－[(3－甲基吡啶－4－基)甲基]吡咯烷－2－酮( 18F－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 18F－SynVesT－1 PET/MR和 18F－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 18F－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 18F－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 18F－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:18F－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。

abstractsObjective:To investigate the application of (4R)-4-(3-[ 18F]fluoranyl-5-fluorophenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one( 18F-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 positive β-amyloid (Aβ) deposition and 20 normal controls (NC; 9 males, 11 females, age (62.6±8.6) years ) without Aβ deposition were retrospectively recruited from Huashan Hospital, Fudan University between December 2021 and December 2022. All of them underwent 18F-SynVesT-1 PET/MR and 18F-Florbetapir (AV45) PET/CT scans. Preprocessing of brain 18F-SynVesT-1 PET images was carried out using statistical parametric mapping (SPM). The differences of the uptke of 18F-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 scores and synaptic density in the lateral temporal lobe ( rs values: 0.71, 0.74, both P<0.001) and medial temporal lobe ( rs values: 0.71, 0.74, both P<0.001). Conclusions:18F-SynVesT-1 PET imaging is a valuable tool for evaluating synaptic density, specifically in the context of AD. The observed widespread reduction in synaptic density across cortical regions of patients with AD are closely related to cognitive decline.