Brain imaging of 18F-fallypride in normal volunteers:: Blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors

Brain imaging of 18F-fallypride in normal volunteers:: Blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors
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DOI:
10.1002/syn.10128
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发表时间:
2002-12-01
期刊:
影响因子:
2.3
通讯作者:
Mantil, J
Mantil, J
中科院分区:
医学4区
文献类型:
--
作者:
Mukherjee, J;Christian, BT;Mantil, J

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在正常志愿者中使用 F-18-fallyphide-PET 对多巴胺 D2/D3 受体进行人体研究,以评估纹状体和纹状体外区域的大脑分布,评估血浆中的代谢物,为这种新型放射性示踪剂建立 PET 成像方案,评估定量 D2/D3 受体的图形分析方法,并评估 F-18-fallypride 以衰老为模型测量 D2/D3 受体变化的能力。受试者(6;21-63 岁)在配备 F-18-fallypride 的西门子 HR+ 扫描仪上进行 PET 扫描,并在 1.5T GE 扫描仪上进行 T1 加权 MRI 扫描,以便与 PET 进行解剖配准。使用 F-18-fallypride (0.07 mCi/Kg) 对每个受试者进行 3 小时 PET 扫描,并在 4-6 周内重复。从所有受试者中获取动脉或动脉化静脉血,以评估血液活性水平并分析血浆中的代谢物。使用 PET 和 PET-MR 配准图像识别并绘制大脑感兴趣区域。使用图形方法分析 PET 数据,其中小脑用作参考区域,提供分布体积比 (DVR),从中导出结合电位 (BP) 并用作受体浓度的测量。 F-18-fallypride 的分布在所有研究对象中是一致的,受体浓度的顺序为壳核 > 尾状核 > 丘脑 = 垂体 > 杏仁核 > 丘 > 黑质 > 海马 = 颞叶皮层 > 顶叶皮层 = 枕叶皮层 = 眶额皮层。对于年轻受试者,血压范围为壳核 37 至眶额皮质 0.4,重测误差约为 10%。在动脉血浆中观察到亲水性和亲脂性代谢物,分析显示大约。 3小时时30-40%的血浆放射性是18F-fallypride。随着年龄的增长,所有大脑区域的 F-18-fallypride 结合力均显着下降(每十年 >10%)。因此,F-18-fallypride 的 PET 研究适合研究纹状体和纹状体外脑区域 D2/D3 受体的变化。 (C) 2002 年威利-利斯。公司
Human studies of dopamine D2/D3 receptors using F-18-fallyphide-PET in normal volunteers were performed to evaluate brain distribution in striatal and extrastriatal regions, evaluate metabolites in blood plasma, establish PET imaging protocol for this new radiotracer, evaluate graphical methods of analysis to quantitate D2/D3 receptors, and assess the ability of F-18-fallypride to measure changes in D2/D3 receptors with aging as a model. Subjects (6; 21-63 years) had a PET scan on a Siemens HR+ scanner with F-18-fallypride and a T1-weighted MRI scan on a 1.5T GE scanner for purposes of anatomical coregistration with PET. A 3-h PET scan with F-18-fallypride (0.07 mCi/Kg) was carried out on each subject and repeated in 4-6 weeks. Arterial or arterialized venous blood was obtained in all subjects in order to evaluate blood activity levels and analyze metabolites in the plasma. Brain regions-of-interest were identified and drawn using PET and PET-MR coregistered images. PET data was analyzed using graphical methods in which cerebellum was used as the reference region providing distribution volume ratios (DVR) from which binding potential (BP) was derived and used as a measure of concentration of receptors. Distribution of F-18-fallypride was consistent in all subjects studied and the rank order of receptor concentration was putamen > caudate > thalamus = pituitary > amygdala > colliculi > substantia nigra > hippocampus = temporal cortex > parietal cortex = occipital cortex = orbitofrontal cortex. For younger subjects, BP ranged from 37 for the putamen to 0.4 for orbitofrontal cortex, with a test-retest error of about 10%. Both hydrophilic and lipophilic metabolites were observed in arterial blood plasma and analyses showed approx. 30-40% of plasma radioactivity at 3 h was 18F-fallypride. With aging, all brain regions exhibited a significant decrease (>10% per decade) in binding of F-18-fallypride. PET studies with F-18-fallypride are thus suitable to study changes in D2/D3 receptors in striatal and extrastriatal brain regions. (C) 2002 Wiley-Liss. Inc.