一种用于非人类灵长类动物线粒体复合体I的新型正电子发射断层显像（PET）放射性配体的表征
Characterization of a novel PET radioligand for mitochondrial complex I in nonhuman primate.
作者信息
Xu Yulong, Xu Yiming, Bagdasarian Frederick Andrew, Dagnew Tewodros Mulugeta, Cheng Hua, Wang Yanli, Wang Yongle, Kang Leyi, Wey Hsiao-Ying, Zhang Can, Zhang Shijun, Wang Changning
机构信息
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States.
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, United States.
出版信息
Nucl Med Biol. 2025 Mar-Apr;142-143:108993. doi: 10.1016/j.nucmedbio.2025.108993. Epub 2025 Jan 10.
The role of mitochondrial complex I (MC-I) dysfunction is well-documented across a range of neurodegenerative disorders. Recently, a novel positron emission tomography (PET) radioligand, [F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [F]CNL02, using nonhuman primate as a model system. In the brain of a rhesus macaque, [F]CNL02 demonstrated specific binding in regions expressing MC-I. All observed brain regions showed rapid kinetic profiles. Analysis of arterial plasma indicated a swift clearance of [F]CNL02 from the bloodstream. Metabolite analysis identified two predominant radiometabolites in the plasma. The regional brain time-activity curves (TACs) for [F]CNL02 were effectively characterized through a two-tissue compartment model (2TCM). Furthermore, the total distribution volume was reliably estimated employing the Logan plot method. Consequently, continued development and refinement of [F]CNL02 are imperative.
线粒体复合物I（MC-I）功能障碍在一系列神经退行性疾病中的作用已有充分记录。最近，一种新型正电子发射断层扫描（PET）放射性配体[F]CNL02已被合成用于靶向MC-I。在本文中，我们以非人灵长类动物为模型系统，对[F]CNL02进行了全面表征。在恒河猴的大脑中，[F]CNL02在表达MC-I的区域表现出特异性结合。所有观察到的脑区都显示出快速的动力学特征。动脉血浆分析表明[F]CNL02能迅速从血液中清除。代谢物分析确定了血浆中的两种主要放射性代谢物。通过双组织隔室模型（2TCM）有效地表征了[F]CNL02的脑区时间-活度曲线（TAC）。此外，采用洛根图法可靠地估计了总分布容积。因此，必须继续开发和优化[F]CNL02。
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