Quantitative analysis of dopamine synthesis in human brain using positron emission tomography with L-[β-11C]DOPA
Quantitative analysis of dopamine synthesis in human brain using positron emission tomography with L-[β-11C]DOPA
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DOI：
10.1097/01.mnm.0000230069.08576.6d
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发表时间：
2006-09-01
影响因子：
1.5
通讯作者：
Suhara, Tetsuya
中科院分区：
文献类型：
--
作者：
Ito, Hiroshi;Ota, Miho;Suhara, Tetsuya
背景和目的 为了估计中枢多巴胺能系统的突触前功能，使用 L-β-C-11]DOPA 或 6-[F-18]氟-L-DOPA 和正电子发射断层扫描测量了内源性多巴胺合成速率。然而，L-β-C-11]DOPA 在人脑中的区域动力学尚未得到详细研究。本研究研究了正常人脑中L-β-C-11]DOPA的区域动力学以及采用参考区域定量L-β-C-11]DOPA动力学方法的准确性。方法静脉注射L-β-C-11]DOPA后，对10名健康受试者进行89分钟的动态扫描。以枕叶皮层为参考脑区，通过动力学和图解法计算总摄取率常数K。结果K的区域分布与多巴胺D-2受体的区域分布相似。血浆中中性氨基酸浓度与通过血脑屏障的流入速率常数（K-1）之间观察到显着的负相关。对于实验数据和模拟数据，图解法计算的K值与动力学方法计算的值非常吻合。结论K的区域分布与黑质纹状体和中脑边缘多巴胺能系统的区域分布相对应。中性氨基酸浓度和 K-1 之间的负相关性支持这样的观点，即左旋多巴通过与中性氨基酸相同的载体系统以竞争方式在血脑屏障处转运。由于图形方法可以消除对动脉输入功能的需要，因此它对于研究神经精神和神经退行性疾病中局部多巴胺合成的速率很有用。
Background and objectives To estimate the presynaptic function of the central dopaminergic system, the rate of endogenous dopamine synthesis has been measured by using L-[beta-C-11]DOPA or 6-[F-18]fluoro-L-DOPA with positron emission tomography. However, the regional kinetics of L-[beta-C-11]DOPA in human brain have not been investigated in detail. In the present study, the regional kinetics of L-[beta-C-11]DOPA in normal human brain and the accuracy of the method for quantifying L-[beta-C-11]DOPA kinetics, employing reference regions, were investigated.Methods After intravenous injection Of L-[beta-C-11]DOPA, dynamic scanning was performed on ten healthy subjects for 89 min. The overall uptake rate constant K Was calculated by the kinetic and graphical approaches, in which the occipital cortex was used as a reference brain region.Results Regional distribution of K was similar to those of dopamine D-2 receptor. A significant negative correlation was observed between the neutral amino acid concentration in plasma and the influx rate constant through the blood-brain barrier (K-1). The K values calculated by graphical approach were in good agreement with the values calculated by kinetic approach for both experimental and simulated data.Conclusions The regional distribution of K corresponds to that of the nigrostriatal and mesolimbic dopaminergic system. Negative correlation between neutral amino acid concentration and K-1 supports the suggestion that L-DOPA is transported in a competitive fashion via the same carrier system as neutral amino acids at the blood-brain barrier. Because the graphical approach can obviate the need for an arterial input function, it is useful for investigating the rate of regional dopamine synthesis in neuropsychiatric and neurodegenerative diseases.