CENTRAL BENZODIAZEPINE RECEPTORS IN HUMAN BRAIN - ESTIMATION OF REGIONAL B(MAX) AND K(D) VALUES WITH POSITRON EMISSION TOMOGRAPHY
CENTRAL BENZODIAZEPINE RECEPTORS IN HUMAN BRAIN - ESTIMATION OF REGIONAL B(MAX) AND K(D) VALUES WITH POSITRON EMISSION TOMOGRAPHY
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DOI：
10.1016/0014-2999(92)90239-z
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发表时间：
1992-03-17
影响因子：
5
通讯作者：
ZARIFIAN, E
中科院分区：
文献类型：
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作者：
ABADIE, P;BARON, JC;ZARIFIAN, E
现在可以使用正电子发射断层扫描 (PET) 和 [C-11] 氟马西尼对人脑中的中枢苯二氮卓受体进行体内研究。为了测量脑区域的 B(max) 和 K(d)，我们使用两次注射 [C-11]氟马西尼（分别在高比放射性和低比放射性）伪平衡范式来评估七名未接受药物治疗的健康志愿者的三种“参考”结构（脑桥、半球白质和胼胝体）的相对优点，其中在注射后 15-40 分钟估计脑组织中的游离放射性配体浓度。静脉注射注射放射性配体。通过高分辨率 PET，根据两点斯卡查德图计算每个受试者 18 个灰质结构的 B(max) 和 K(d)。我们发现使用胼胝体作为参考通常会导致虚假的 B(max) 和 K(d) 值。脑桥是最好的参考结构，因为它提供了令人满意的 B(max) 值（最接近体外数据）和最一致的 K(d) 值，并且是 PET 图像上最容易采样的区域。区域 B(max) 的模式与体外研究的预期一致，大脑皮层的值最高，小脑的值居中，纹状体和丘脑的值最低。 K(d) 值在区域之间是一致的，并且与早期的体外和体内数据一致。这项工作证明了估计多个大脑区域中枢苯二氮卓受体的 B(m)ax 和 K(d) 用于临床研究的可行性。
Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [C-11]flumazenil. With the aim of measuring B(max) and K(d) in brain regions, we used a two-injection [C-11]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the B(max) and K(d) were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious B(max) and K(d) values. The pons was the best reference structure because it provided satisfactory B(max) values (closest to in vitro data) and most consistent K(d) values, and was the region easiest to sample on PET images. The pattern of regional B(max) was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The K(d) values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating B(m)ax and K(d) of central benzodiazepine receptors in multiple brain regions for clinical research.