Chinical application of synaptic vesicle protein 2A radioactive tracer 18F-SynVesT-1 in patients with Alzheimer's disease
Objective To investigate the application of(4R)-4-(3-[68G]fluoranyl-5-fluorophe-nyl)-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 retrospec-tively 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 68G-SynVesT-1 PET images was carried out using statistical parametric mapping(SPM).The differ-ences 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 anal-ysis,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 re-gions(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±0.13vs 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.
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