Lassen N A, Bartenstein P A, Lammertsma A A, Prevett M C, Turton D R, Luthra S K, Osman S, Bloomfield P M, Jones T, Patsalos P N
Department of Clinical Physiology, Nuclear Medicine, Bispebjerg Hospital, Copenhagen, Denmark.
J Cereb Blood Flow Metab. 1995 Jan;15(1):152-65. doi: 10.1038/jcbfm.1995.17.
Carbon-11-labeled flumazenil combined with positron emission tomography (PET) was used to measure the concentration (Bmax) of the benzodiazepine (Bz) receptor in the brain and its equilibrium dissociation constant (KD) 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 2h before the bolus tracer injection and continuing until the end of 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 KD value of 12 nM/L of water and Bmax 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 KD but lower Bmax values than the steady-state approach presented here.
采用碳-11标记的氟马西尼结合正电子发射断层扫描（PET）技术，对5名正常受试者大脑中苯二氮䓬（Bz）受体的浓度（Bmax）及其对氟马西尼的平衡解离常数（KD）进行了测量。采用稳态法，以高比活度的团注形式注射示踪剂。对每名受试者进行了两项研究。第一项研究在受体占有率基本为零时进行，即仅注射示踪剂的研究。第二项研究在受体占有率约为50%的稳态下进行，通过在团注示踪剂注射前2小时开始持续输注未标记的（“冷”）氟马西尼，并持续至扫描期结束来实现。在第二项研究中，对多个血样中血浆水内未代谢氟马西尼的游离浓度进行了测量。以每毫米相同放射性单位校准后的观察到的组织和血浆示踪剂曲线，通过两种方式进行分析：（a）采用非房室（随机）方法，不对组织中的房室数量做任何假设；（b）采用单房室方法，假设示踪剂在所有组织房室之间快速交换（混合）。非房室分析和房室分析得出的示踪剂分布容积值基本相同，该参数用于定量Bz受体。由于房室方法可应用于更短的观察期（60分钟而非120分钟），因此更受青睐。5名受试者的平均KD值为12 nM/L水，灰质的Bmax值范围为丘脑的39±11至枕叶皮质脑的120±14 nM/L。此前的大多数研究基于伪平衡法，以脑干作为无受体参考区域。与本文介绍的稳态法相比，这种方法得出的KD值实际上相同，但Bmax值更低。
