Asai Yoshiyuki, Ikoma Yoko, Takano Akihiro, Maeda Jun, Toyama Hinako, Yasuno Fumihiko, Ichimiya Tetsuya, Ito Hiroshi, Suhara Tetsuya
Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
Nucl Med Commun. 2009 Nov;30(11):872-80. doi: 10.1097/MNM.0b013e32833019bf.
Gamma-aminobutyric acid (GABA)A/benzodiazepine (BZ) receptor chloride channel consists of several subunits. The diversity of the α subunits results in the various ligand selectivity and functionally different properties of the GABAA/BZ receptor. Although [¹¹C] Ro15-4513 is reported to be a radioligand that has relatively high affinity for α5 subunit-containing GABAA/BZ receptor, it remained to be evaluated fully.
The aim of this study was to evaluate the quantitative analyses of [¹¹C]Ro15-4513 in the living human brain.
Positron emission tomography examinations were performed in eight healthy male volunteers after intravenous injection of [¹¹C]Ro15-4513. Kinetic analysis of data was performed with the two-compartment and three-compartment models using arterial input function. Linear graphical analysis and the simplified reference tissue model analysis (SRTM) were also performed using pons as a reference region. In a simulation study, the effects of noise to the estimation of binding potentials were evaluated.
The accumulation of [¹¹C]Ro15-4513 in the limbic system was relatively higher than in other cortex. The bindings were well described by the three-compartment model in the regions with specific binding. Binding potentials obtained from the graphical method and SRTM correlated well with those obtained from the three-compartment model. In the simulation study, estimated parameters from SRTM were less affected by noise compared with those from the graphical method.
The reference tissue methods using pons as a reference region can be used for quantitative analysis of [¹¹C]Ro15-4513 binding. SRTM seemed less susceptible to noise than does graphical analysis.
γ-氨基丁酸（GABA）A/苯二氮䓬（BZ）受体氯离子通道由多个亚基组成。α亚基的多样性导致GABAA/BZ受体具有不同的配体选择性和功能特性。尽管据报道[¹¹C]Ro15 - 4513是一种对含α5亚基的GABAA/BZ受体具有相对高亲和力的放射性配体，但仍有待全面评估。
本研究旨在评估[¹¹C]Ro15 - 4513在活体人脑中的定量分析。
对8名健康男性志愿者静脉注射[¹¹C]Ro15 - 4513后进行正电子发射断层扫描检查。使用动脉输入函数，采用二室和三室模型对数据进行动力学分析。还以脑桥作为参考区域进行线性图形分析和简化参考组织模型分析（SRTM）。在模拟研究中，评估了噪声对结合电位估计的影响。
[¹¹C]Ro15 - 4513在边缘系统中的蓄积相对高于其他皮质。三室模型能很好地描述具有特异性结合区域的结合情况。通过图形法和SRTM获得的结合电位与三室模型获得的结果相关性良好。在模拟研究中，与图形法相比，SRTM估计的参数受噪声影响较小。
以脑桥作为参考区域的参考组织方法可用于[¹¹C]Ro15 - 4513结合的定量分析。SRTM似乎比图形分析更不易受噪声影响。
