PDF(Pubmed)
Abstract：
PET imaging of synaptic vesicle glycoprotein 2A allows for noninvasive quantification of synapses. This first-in-human study aimed to evaluate the kinetics, test-retest reproducibility, and extent of specific binding of a recently developed synaptic vesicle glycoprotein 2A PET ligand, (R)-4-(3-(18F-fluoro)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidine-2-one (18F-SynVesT-2), with fast brain kinetics. Methods: Nine healthy volunteers participated in this study and were scanned on a High Resolution Research Tomograph scanner with 18F-SynVesT-2. Five volunteers were scanned twice on 2 different days. Five volunteers were rescanned with preinjected levetiracetam (20 mg/kg, intravenously). Arterial blood was collected to calculate the plasma free fraction and generate the arterial input function. Individual MR images were coregistered to a brain atlas to define regions of interest for generating time-activity curves, which were fitted with 1- and 2-tissue-compartment (1TC and 2TC) models to derive the regional distribution volume (V T). The regional nondisplaceable binding potential (BP ND) was calculated from 1TC V T, using the centrum semiovale (CS) as the reference region. Results: 18F-SynVesT-2 was synthesized with high molar activity (187 ± 69 MBq/nmol, n = 19). The parent fraction of 18F-SynVesT-2 in plasma was 28% ± 8% at 30 min after injection, and the plasma free fraction was high (0.29 ± 0.04). 18F-SynVesT-2 entered the brain quickly, with an SUVpeak of 8 within 10 min after injection. Regional time-activity curves fitted well with both the 1TC and the 2TC models; however, V T was estimated more reliably using the 1TC model. The 1TC V T ranged from 1.9 ± 0.2 mL/cm3 in CS to 7.6 ± 0.8 mL/cm3 in the putamen, with low absolute test-retest variability (6.0% ± 3.6%). Regional BP ND ranged from 1.76 ± 0.21 in the hippocampus to 3.06 ± 0.29 in the putamen. A 20-min scan was sufficient to provide reliable V T and BP ND Conclusion: 18F-SynVesT-2 has fast kinetics, high specific uptake, and low nonspecific uptake in the brain. Consistent with the nonhuman primate results, the kinetics of 18F-SynVesT-2 is faster than the kinetics of 11C-UCB-J and 18F-SynVesT-1 in the human brain and enables a shorter dynamic scan to derive physiologic information on cerebral blood flow and synapse density.
摘要：
突触小泡糖蛋白2A的PET成像允许突触的非侵入性定量。这项首次在人类中的研究旨在评估动力学，复测重现性，以及最近开发的突触小泡糖蛋白2APET配体的特异性结合程度，(R)-4-(3-(18F-氟)苯基)-1-((3-甲基吡啶-4-基)甲基)吡咯烷-2-酮(18F-SynVesT-2),具有快速的大脑动力学。方法：9名健康志愿者参加了这项研究，并在高分辨率研究断层扫描仪上使用18F-SynVesT-2进行了扫描。5名志愿者在不同的2天扫描2次。五名志愿者接受预注射左乙拉西坦(20mg/kg，静脉注射)。收集动脉血以计算血浆游离分数并生成动脉输入函数。将各个MR图像与大脑图集进行配准，以定义用于生成时间-活动曲线的感兴趣区域，用1-和2-组织区室（1TC和2TC）模型拟合，得出区域分布体积（VT）。从1TCVT计算区域不可位移结合电位(BPND)，使用中心半卵（CS）作为参考区域。结果:合成的18F-SynVesT-2具有较高的摩尔活性(187±69MBq/nmol,n=19)。血浆中18F-SynVesT-2的母体分数在注射后30分钟为28%±8%，血浆游离分数高（0.29±0.04）。18F-SynVesT-2迅速进入大脑，在注射后10分钟内SUVpeak为8。区域时间-活动曲线与1TC和2TC模型拟合良好；然而，使用1TC模型更可靠地估计了VT。1TCVT范围从CS的1.9±0.2mL/cm3到壳核的7.6±0.8mL/cm3，具有较低的绝对重测变异性（6.0％±3.6％）。区域BPND范围从海马的1.76±0.21到壳核的3.06±0.29。20分钟的扫描足以提供可靠的VT和BPND结论：18F-SynVesT-2具有快速的动力学，高比摄取，和大脑中的低非特异性摄取。与非人类灵长类动物的结果一致，在人脑中,18F-SynVesT-2的动力学比11C-UCB-J和18F-SynVesT-1的动力学更快,并且能够在较短的动态扫描中获得脑血流和突触密度的生理信息.
