A Two-Compartment Description and Kinetic Procedure for Measuring Regional Cerebral [11C]Nomifensine Uptake Using Positron Emission Tomography
A Two-Compartment Description and Kinetic Procedure for Measuring Regional Cerebral [11C]Nomifensine Uptake Using Positron Emission Tomography
复制标题
使用正电子发射断层扫描测量区域脑 [11C]诺米芬辛摄取的两室描述和动力学程序
DOI：
--
复制
发表时间：
1990
影响因子：
6.3
通讯作者：
Richard S. J. Frackowiak
中科院分区：
文献类型：
--
作者：
E. Salmon;D. Brooks;K. Leenders;D. Turton;S. Hume;J. E. Cremer;T. Jones;Richard S. J. Frackowiak
S-[11 C]诺米芬辛（S-[11 C]NMF）是一种适用于正电子发射断层扫描的正电子发射示踪剂，可与纹状体和丘脑中的多巴胺能和去甲肾上腺素能重摄取位点结合。由于血浆中葡萄糖醛酸苷代谢产物的快速出现，阻碍了该药物的脑分布建模，而葡萄糖醛酸苷代谢产物不会穿过血脑屏障。到目前为止，[11 C]NMF摄取只是表示为区域与非特异性小脑活动比率。我们根据红细胞活性曲线计算了“游离”NMF输入曲线，利用游离药物在红细胞和血浆之间迅速平衡的事实，而葡萄糖醛酸苷不进入红细胞。利用该自由[11 C]NMF输入函数，所有局部脑摄取曲线可以拟合到传统的二室模型，根据[11 C]NMF局部分布容积定义示踪剂分布。假设小脑的[11 C]NMF的分布体积代表纹状体和丘脑中示踪剂的非特异性分布体积，我们计算了[11 C]NMF在这些区域中自由交换的特异性和非特异性隔室之间的平衡分配系数，代表其与多巴胺能或去甲肾上腺素能摄取位点（或复合物）的“结合潜力”。当给予外消旋体而不是[11 C]NMF的活性S-对映体时，纹状体中的分配系数较低。在帕金森病和多系统萎缩患者的纹状体中，与年龄匹配的志愿者相比，S-[11 C]NMF的特异性区室化显著降低。
S-[11C]Nomifensine (S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood–brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a “free” NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its “binding potential” to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers.