Kinetic analysis of the translocator protein positron emission tomography ligand [(18)F]GE-180 in the human brain.
Kinetic analysis of the translocator protein positron emission tomography ligand [(18)F]GE-180 in the human brain.
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DOI：
10.1007/s00259-016-3444-z
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发表时间：
2016-11
影响因子：
9.1
通讯作者：
Sharp, David J.
中科院分区：
文献类型：
--
作者：
Feeney, Claire;Scott, Gregory;Raffel, Joel;Roberts, S.;Coello, Christopher;Jolly, Amy;Searle, Graham;Goldstone, A. P.;Brooks, David J.;Nicholas, Richard S.;Trigg, William;Gunn, Roger N.;Sharp, David J.
PET可以通过靶向转运蛋白（TSPO）来成像神经炎症，TSPO在活化的小胶质细胞中上调。第一代TSPO放射配体[11C]PK-11195的高非特异性结合限制了准确的定量。[18F]GE-180是一种新型的TSPO配体，在体外与[11C]PK-11195表现出良好的结合。我们的目的是：(1)评估健康人大脑中[18F]GE-180的示踪剂特征；(2)研究TSPO Ala147Thr多态性是否影响结果测量。在注射[18F]GE-180后，10名志愿者（5种高亲和力结合物，hab和5种混合亲和力结合物，mab）进行了动脉采样的动态PET扫描。采用单组织和双组织室室模型对时间-活动曲线进行动力学建模，并用Logan图形分析对数据进行分析。主要结果测量是不同兴趣区域（roi）的总分布量（VT）。次要结局指标是标准化摄取值（SUV）、分布体积和使用伪参考区域估计的SUV比率。双组织室模型为最佳模型。平均区域递送速率常数（K1）为0.01 mL cm−3 min−1，表明通过血脑屏障的提取率较低（1%）。所有roi的估计中位VT也很低，纹状体为0.16 mL cm - 3，丘脑为0.38 mL cm - 3。在所有roi中，赤潮抗体和单克隆抗体之间的VT无显著差异。可逆的两组织室模型很好地拟合了数据，并确定示踪剂在健康个体中具有较低的第一次提取率（约1%）和较低的VT估计。与其他第二代TSPO PET示踪剂相比，没有观察到对rs6971多态性的依赖性。需要对神经炎性疾病人群中的[18F]GE-180进行研究，以确定其用于定量评估TSPO表达的适用性。本文的在线版本（doi:10.1007/s00259-016-3444-z）包含补充材料，仅供授权用户使用。
PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [11C]PK-11195 limits accurate quantification. [18F]GE-180, a novel TSPO ligand, displays superior binding to [11C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [18F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [18F]GE-180. Kinetic modelling of time–activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (VT) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. The two-tissue compartment model was the best model. The average regional delivery rate constant (K1) was 0.01 mL cm−3 min−1 indicating low extraction across the blood–brain barrier (1 %). The estimated median VT across all ROIs was also low, ranging from 0.16 mL cm−3 in the striatum to 0.38 mL cm−3 in the thalamus. There were no significant differences in VT between HABs and MABs across all ROIs. A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low VT estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [18F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression. The online version of this article (doi:10.1007/s00259-016-3444-z) contains supplementary material, which is available to authorized users.
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影响因子：
9.9
作者：
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通讯作者：
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影响因子：
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