Mitochondrial complex 1 is involved in maintaining brain bioenergetics; σ-1 receptor responds to neuronal stress; and synaptic vesicle protein 2A reflects synaptic integrity. Expression of each of these proteins is altered in neurodegenerative diseases. Here, we characterize the kinetic behavior of 3 PET radioligands-18F-BCPP-EF, 11C-SA-4503, and 11C-UCB-J-for the measurement of mitochondrial complex 1, σ-1 receptor, and synaptic vesicle protein 2A, respectively, and determine appropriate analysis workflows for their application in future studies of the in vivo molecular pathology of these diseases. Methods: Twelve human subjects underwent dynamic PET scans with each radioligand, including associated arterial blood sampling. A range of kinetic models was investigated to identify an optimal kinetic analysis method for each radioligand and a suitable acquisition duration. Results: All 3 radioligands readily entered the brain and yielded heterogeneous uptake consistent with the known distribution of the targets. The optimal models determined for the regional estimates of volume of distribution were multilinear analysis 1 (MA1) and the 2-tissue-compartment model for 18F-BCPP-EF, MA1 for 11C-SA-4503, and both MA1 and the 1-tissue-compartment model for 11C-UCB-J. Acquisition times of 70, 80, and 60 min for 18F-BCPP-EF, 11C-SA-4503, 11C-UCB-J, respectively, provided good estimates of regional volume of distribution values. An effect of age was observed on 18F-BCPP-EF and 11C-UCB-J signal in the caudate. Conclusion: These ligands can be assessed for their potential to stratify patients or monitor the progression of molecular neuropathology in neurodegenerative diseases.

中文翻译：

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定量用于健康人脑中线粒体和突触功能的3种PET示踪剂的表征：18F-BCPP-EF，11C-SA-4503和11C-UCB-J。

线粒体复合物1参与维持脑生物能。σ-1受体对神经元压力有反应；突触小泡蛋白2A反映突触完整性。这些蛋白质各自的表达在神经退行性疾病中发生改变。在这里，我们表征了3种PET放射性配体18F-BCPP-EF，11C-SA-4503和11C-UCB-J的动力学行为，用于测量线粒体复合物1，σ-1受体和突触小泡蛋白2A，并确定适当的分析工作流程，以将其应用在这些疾病的体内分子病理学的未来研究中。方法：对十二名人类受试者的每个放射性配体进行动态PET扫描，包括相关的动脉血采样。研究了一系列动力学模型，以确定每种放射性配体的最佳动力学分析方法和合适的采集时间。结果：所有3种放射性配体均易于进入大脑，并产生与靶标已知分布一致的异质摄取。确定区域分布量的最佳模型是多线性分析1（MA1）和18F-BCPP-EF的2组织隔间模型，11C-SA-4503的MA1以及MA1和1组织11C-UCB-J的车厢模型。18F-BCPP-EF，11C-SA-4503、11C-UCB-J的采集时间分别为70、80和60分钟，可以很好地估算区域分布值。在尾状体中观察到年龄对18F-BCPP-EF和11C-UCB-J信号的影响。结论：