Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Research Institute, Montreal, Quebec, Canada.
Synapse. 2012 Jun;66(6):552-60. doi: 10.1002/syn.21542. Epub 2012 Mar 16.
This study evaluates the reproducibility of the quantification of metabotropic glutamate receptor type 5 (mGluR₅) densities in rats using the PET radiotracer [¹¹C]ABP688 and pharmacokinetic models that are based on an input function, which is derived from a reference tissue. Seven rats underwent dynamic PET scans (60 min) after bolus injection of [¹¹C]ABP688. Kinetic analyses included: binding potential (BP(ND) ) determined by calculating (a) the simplified reference tissue model (SRTM) and (b) its two-steps simplified version (SRTM2); (c) multilinear reference tissue model (MRTM) and (d) its 2-parameter version (MRTM2); (e) noninvasive graphical analysis (NIGA). Parametric images were generated representing BP(ND) by the MRTM2 model. BP(ND) determinations were reproducible with low to acceptable variability ranging from 5 to 10% and reproducibility scores (intraclass correlation coefficient) between 0.51 and 0.88. The pharmacokinetic model that showed lowest overall variability was the SRTM. In contrast, the use of the NIGA was associated with significantly lower reproducibility scores. Comparison of parametric images revealed no significant bias between test and retest measurements and is therefore suitable to compare groups at voxel levels. In conclusion, our results suggest that noninvasive quantification of [¹¹C]ABP688 imaging is reproducible and reliable for PET studies of the cerebral mGluR₅ in rats.
本研究评估了使用 PET 示踪剂 [¹¹C]ABP688 和基于参考组织的输入函数的药代动力学模型来定量大鼠代谢型谷氨酸受体 5 (mGluR₅) 密度的重现性。7 只大鼠在静脉注射 [¹¹C]ABP688 后进行了动态 PET 扫描(60 分钟)。动力学分析包括:通过计算(a)简化参考组织模型(SRTM)和(b)其两步简化版本(SRTM2)来确定结合潜力(BP(ND));(c)多线性参考组织模型(MRTM)和(d)其 2-参数版本(MRTM2);(e)无创图形分析(NIGA)。通过 MRTM2 模型生成表示 BP(ND)的参数图像。BP(ND)的测定具有低至可接受的变异性,范围为 5%至 10%,重现性评分(组内相关系数)在 0.51 至 0.88 之间。总体变异性最低的药代动力学模型是 SRTM。相比之下,使用 NIGA 与显著较低的重现性评分相关。参数图像的比较显示,测试和复测测量之间没有显著的偏差,因此适合在体素水平上比较组间差异。总之,我们的结果表明,[¹¹C]ABP688 成像的无创定量对于大鼠脑 mGluR₅ 的 PET 研究是可重复和可靠的。