Kinetic analysis and test-retest variability of the radioligand [11C](R)-PK11195 binding to TSPO in the human brain - a PET study in control subjects
Kinetic analysis and test-retest variability of the radioligand [11C](R)-PK11195 binding to TSPO in the human brain - a PET study in control subjects
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DOI：
10.1186/2191-219x-2-15
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发表时间：
2012-01-01
期刊：
影响因子：
3.2
通讯作者：
Farde, Lars
中科院分区：
文献类型：
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作者：
Jucaite, Aurelija;Cselenyi, Zsolt;Farde, Lars
背景：正电子发射断层扫描和放射配体[C-11](R)-PK11195已被用于转运蛋白（TSPO）的成像，并用于绘制神经精神疾病患者脑内的小胶质细胞。[C-11](R)-PK11195结合已经使用参考区域方法进行了量化，参考区域通过解剖学定义或使用无监督或有监督聚类算法。到目前为止，动力学隔室模型还没有提出。在目前的重测研究中，我们详细研究了[C-11](R)-PK11195结合的特征，使用经典的带有代谢物校正的动脉输入函数的室分析。方法：在6名对照受试者中，间隔6周两次检测[C-11](R)-PK11195结合情况。采用Akaike标准和f统计量比较单组织和双组织腔室模型（1、2中药）的结果。结合电位（BPND）估计的可重复性通过测量差异（误差百分比）和类内相关系数（ICCs）来评估。结果：[C-11](R)-PK11195结合可以用2TCM描述，2TCM是首选模型。测量误差（以百分比为单位）表明，在大的大脑区域（平均误差：全脑4%，灰质5%）具有良好的再现性，但在较小的皮层下区域（壳核25%，尾状核55%）则没有。ICC值中低，白质最高（0.73），全脑和丘脑最高（0.57），皮质灰质最高（0.47）。相当大[C-11](R)-PK11195 BPND可以在整个人脑中被识别（范围1.11至2.21）。结论：[C-11](R)-PK11195结合的高受试者内部变异性限制了TSPO变化的纵向监测。2TCM对[C-11](R)-PK11195结合的解释表明，在生理条件下不能排除与TSPO特异性结合的存在。
Background: Positron-emission tomography and the radioligand [C-11](R)-PK11195 have been used for the imaging of the translocator protein (TSPO) and applied to map microglia cells in the brain in neuropsychiatric disorders. [C-11](R)-PK11195 binding has been quantified using reference region approaches, with the reference defined anatomically or using unsupervised or supervised clustering algorithms. Kinetic compartment modelling so far has not been presented. In the present test-retest study, we examine the characteristics of [C-11](R)-PK11195 binding in detail, using the classical compartment analysis with a metabolite-corrected arterial input function.Methods: [C-11](R)-PK11195 binding was examined in six control subjects at two separate occasions, 6 weeks apart. Results of one-tissue and two-tissue compartment models (1TCM, 2TCM) were compared using the Akaike criteria and F-statistics. The reproducibility of binding potential (BPND) estimates was evaluated by difference in measurements (error in percent) and intraclass correlation coefficients (ICCs).Results: [C-11](R)-PK11195 binding could be described by 2TCM which was the preferred model. Measurement error (in percent) indicated good reproducibility in large brain regions (mean error: whole brain 4%, grey matter 5%), but not in smaller subcortical regions (putamen 25%, caudate 55%). The ICC values were moderate to low, highest for the white matter (0.73), whole brain and thalamus (0.57), and cortical grey matter (0.47). Sizeable [C-11](R)-PK11195 BPND could be identified throughout the human brain (range 1.11 to 2.21).Conclusions: High intra-subject variability of [C-11](R)-PK11195 binding limits longitudinal monitoring of TSPO changes. The interpretation of [C-11](R)-PK11195 binding by 2TCM suggests that the presence of specific binding to TSPO cannot be excluded at physiological conditions.