Mukherjee Jogeshwar, Christian Bradley T, Dunigan Kelly A, Shi Bingzhi, Narayanan Tanjore K, Satter Martin, Mantil Joseph
Department of Nuclear Medicine/PET, Kettering Medical Center, Dayton, Ohio 45429, USA.
Synapse. 2002 Dec 1;46(3):170-88. doi: 10.1002/syn.10128.
Human studies of dopamine D2/D3 receptors using 18F-fallypride-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 18F-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 18F-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 18F-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 18F-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 18F-fallypride. PET studies with 18F-fallypride are thus suitable to study changes in D2/D3 receptors in striatal and extrastriatal brain regions.
在正常志愿者中开展了使用18F-法螺必利正电子发射断层扫描（PET）对多巴胺D2/D3受体的人体研究，以评估纹状体和纹状体以外区域的脑部分布，评估血浆中的代谢物，建立这种新型放射性示踪剂的PET成像方案，评估用于定量D2/D3受体的图形分析方法，并以衰老为模型评估18F-法螺必利测量D2/D3受体变化的能力。受试者（6名；21 - 63岁）在西门子HR +扫描仪上进行了18F-法螺必利PET扫描，并在1.5T通用电气扫描仪上进行了T1加权磁共振成像（MRI）扫描，以便与PET进行解剖学配准。对每位受试者进行了一次3小时的18F-法螺必利（0.07毫居里/千克）PET扫描，并在4 - 6周后重复进行。在所有受试者中采集动脉血或动脉化静脉血，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脑感兴趣区域。PET数据采用图形分析方法进行分析，其中以小脑作为参考区域，提供分布容积比（DVR），从中得出结合潜力（BP）并用作受体浓度的度量。在所有研究的受试者中，18F-法螺必利的分布是一致的，受体浓度的排序为壳核＞尾状核＞丘脑 = 垂体＞杏仁核＞丘系＞黑质＞海马 = 颞叶皮质＞顶叶皮质 = 枕叶皮质 = 眶额皮质。对于较年轻的受试者，壳核的BP范围为37，眶额皮质为0.4，重测误差约为10%。在动脉血浆中观察到了亲水性和亲脂性代谢物，分析表明在3小时时血浆放射性的约30 - 40%为18F-法螺必利。随着年龄增长，所有脑区的18F-法螺必利结合均显著下降（每十年＞10%）。因此，使用18F-法螺必利的PET研究适用于研究纹状体和纹状体以外脑区D2/D3受体的变化。
