Yamasaki Tomoteru, Maeda Jun, Fujinaga Masayuki, Nagai Yuji, Hatori Akiko, Yui Joji, Xie Lin, Nengaki Nobuki, Zhang Ming-Rong
Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences Inage-ku, Chiba, Japan.
Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences Inage-ku, Chiba, Japan.
Am J Nucl Med Mol Imaging. 2014 Apr 25;4(3):260-9. eCollection 2014.
The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed (11)C-labeled PET probes (11)C-ITMM and (11)C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared (11)C-ITMM and (11)C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with (11)C-ITDM than with (11)C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm(-3) for (11)C-ITMM and 3.6 mL∙cm(-3) for (11)C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of (11)C-ITMM and (11)C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that (11)C-ITDM may be superior to (11)C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with (11)C-ITDM were higher than those of (11)C-ITMM. Clinical studies of (11)C-ITDM in humans will be necessary in the future.
代谢型谷氨酸受体1（mGluR1）是开发治疗中枢神经系统疾病新药的新型靶蛋白。最近，我们开发了具有相似特性的（11）C标记的PET探针（11）C - ITMM和（11）C - ITDM，用于mGluR1成像。在本研究中，我们比较了（11）C - ITMM和（11）C - ITDM在猴脑中的PET成像和定量分析。各自的PET图像显示在小脑、丘脑和扣带回皮质中摄取分布相似。检测到（11）C - ITDM的摄取略高于（11）C - ITMM。对于使用双组织室模型（2 - TCM）的动力学分析，小脑（脑中富含mGluR1的区域）中（11）C - ITMM的分布容积（VT）为2.5 mL∙cm（-3），（11）C - ITDM为3.6 mL∙cm（-3）。相比之下，对于两种放射性药物，脑桥（mGluR1表达可忽略不计的区域）中的VT同样较低。基于这些结果，我们使用脑桥的时间 - 活性曲线作为参考区域，通过通用参考组织模型进行了非侵入性PET定量分析。我们使用相关散点图和Bland - Altman图分析确认了参考组织模型与2 - TCM之间的关系和差异。尽管两种放射性药物的散点图均显示基于参考组织模型的结合潜能相对于2 - TCM存在高估或低估，但两种动力学分析模型之间无显著差异。总之，我们首次证明了（11）C - ITMM和（11）C - ITDM使用参考组织模型进行非侵入性PET定量分析的潜力。此外，我们的研究结果表明，作为mGluR1成像的PET探针，（11）C - ITDM可能优于（11）C - ITMM，因为（11）C - ITDM的PET区域VT值高于（11）C - ITMM。未来有必要对（11）C - ITDM进行人体临床研究。
