Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans
Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans
复制标题
DOI：
10.1177/0271678x17724947
复制
发表时间：
2018-11-01
影响因子：
6.3
通讯作者：
Carson, Richard E.
中科院分区：
文献类型：
--
作者：
Finnema, Sjoerd J.;Nabulsi, Nabeel B.;Carson, Richard E.
突触囊泡糖蛋白2A（SV 2A）广泛存在于突触前末梢。在这里，我们报告了人体中SV 2A正电子发射断层扫描（PET）放射性配体[C-11]UCB-J的动力学建模和重测重现性评估。5名志愿者在静脉注射[C-11]UCB-J后进行两次高分辨RT检查，采集动脉血用于放射性代谢和游离分数的测量。采用1-组织（1 T）和2-组织（2 T）房室模型分析局部时间-活性曲线，以估计分布容积（V-T）。使用1 T模型生成参数图。[C-11]UCB-J代谢相当快，注射后15分钟母体分数为36 +/- 13%。血浆游离分数为32 +/-1%。区域的时间-活性曲线显示快速的动力学，并很好地描述了1 T模型，除了小脑和海马。用2 T模型估计的V-T值与1 T值相似。参数图是高质量的，V-T值与基于时间活动曲线（TAC）的估计值相关性良好。采集时间从120 min缩短至60 min对V-T值的影响可忽略不计。各地区V-T的平均绝对重测重现性为3-9%。总之，[C-11]UCB-J表现出优异的PET示踪剂特性，并有潜力作为测量神经退行性疾病中突触密度的通用工具。
Synaptic vesicle glycoprotein 2A (SV2A) is ubiquitously present in presynaptic terminals. Here we report kinetic modeling and test-retest reproducibility assessment of the SV2A positron emission tomography (PET) radioligand [C-11]UCB-J in humans. Five volunteers were examined twice on the HRRT after bolus injection of [C-11]UCB-J. Arterial blood samples were collected for measurements of radiometabolites and free fraction. Regional time-activity curves were analyzed with 1-tissue (1T) and 2-tissue (2T) compartment models to estimate volumes of distribution (V-T). Parametric maps were generated using the 1T model. [C-11]UCB-J metabolized fairly quickly, with parent fraction of 36 +/- 13% at 15 min after injection. Plasma free fraction was 32 +/- 1%. Regional time-activity curves displayed rapid kinetics and were well described by the 1T model, except for the cerebellum and hippocampus. V-T values estimated with the 2T model were similar to 1T values. Parametric maps were of high quality and V-T values correlated well with time activity curve (TAC)-based estimates. Shortening of acquisition time from 120 min to 60 min had a negligible effect on V-T values. The mean absolute test-retest reproducibility for V-T was 3-9% across regions. In conclusion, [C-11]UCB-J exhibited excellent PET tracer characteristics and has potential as a general purpose tool for measuring synaptic density in neurodegenerative disorders.