BENZODIAZEPINE RECEPTOR QUANTIFICATION IN-VIVO IN HUMANS USING [C-11] FLUMAZENIL AND PET - APPLICATION OF THE STEADY-STATE PRINCIPLE
BENZODIAZEPINE RECEPTOR QUANTIFICATION IN-VIVO IN HUMANS USING [C-11] FLUMAZENIL AND PET - APPLICATION OF THE STEADY-STATE PRINCIPLE
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DOI：
10.1038/jcbfm.1995.17
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发表时间：
1995-01-01
影响因子：
6.3
通讯作者：
ANDERSEN, JV
中科院分区：
文献类型：
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作者：
LASSEN, NA;BARTENSTEIN, PA;ANDERSEN, JV
采用碳11标记氟马西尼结合正电子发射断层扫描（PET）技术测定了5名正常人脑内苯二氮卓（Bz）受体的浓度（B-max）及其对氟马西尼的平衡解离常数（K-D）。稳态方法采用注射示踪剂作为高比活性的丸剂。在每个主题中进行了两项研究。第一项研究基本上是在零受体占用的情况下进行的，即单独使用示踪剂的研究。第二项研究是在约50%的稳态受体占用下进行的，通过在大剂量示踪剂注射前2小时开始长时间持续输注无标记（“冷”）氟马西尼，一直持续到扫描期结束。在第二项研究中，测量了多个血液样本血浆水中未代谢氟马西尼的游离浓度。观察到的组织和血浆示踪剂曲线，以相同的每毫米放射性单位校准，以两种方式进行分析：(a)通过非隔室（随机）方法，不假设组织中的隔室数量，(b)通过单隔室方法，假设所有组织隔室之间的示踪剂快速交换（混合）。非区室分析和区室分析对用于定量Bz受体的示踪剂的分布体积给出了基本相同的值。由于区室法可以应用于更短的观察时间（60分钟而不是120分钟），因此是首选方法。5名受试者水的平均K-D值为12 nM/L，脑灰质的B-max值从丘脑的39 +/- 11到枕叶皮层的120 +/- 14 nM/L不等。大多数先前的研究都是基于假平衡方法，使用脑干作为无受体参考区域。这产生了几乎相同的K-D，但B-max值低于这里提出的稳态方法。
Carbon-11-labeled flumazenil combined with positron emission tomography (PET) was used to measure the concentration (B-max) of the benzodiazepine (Bz) receptor in the brain and its equilibrium dissociation constant (K-D) for flumazenil in five normal subjects. The steady-state approach was used injecting the tracer as a bolus of high specific activity. In each subject two studies were carried out. The first study was performed at essentially zero receptor occupancy, the tracer alone study. The second study was performed at a steady-state receptor occupancy of about 50%, achieved by a prolonged constant infusion of nonlabeled (''cold'') flumazenil starting 2 h before the bolus tracer injection and continuing until the end of the scanning period. In this second study the free concentration of unmetabolized flumazenil in plasma water was measured in multiple blood samples. The observed tissue and plasma tracer curves, calibrated in the same units of radioactivity per millimeter, were analyzed in two ways: (a) by the noncompartmental (stochastic) approach making no assumptions regarding number of compartments in the tissue, and (b) by the single-compartment approach assuming rapid exchange (mixing) of tracer between all tissue compartments. The noncompartmental and the compartmental analyses gave essentially the same values for the distribution volume of the tracer, the parameter used for quantitation of the Bz receptor. As the compartmental approach could be applied to a shorter observation period (60 min instead of 120 min) it was preferred. The five subjects had a mean K-D value of 12 nM/L of water and B-max values of the grey matter ranging from 39 +/- 11 in thalamus to 120 +/- 14 nM/L of brain in occipital cortex. Most previous studies have been based on the pseudoequilibrium approach using the brain stem as a receptor-free reference region. This yields practically the same K-D but lower B-max values than the steady-state approach presented here.