Characterization of a novel PET radioligand for mitochondrial complex I in nonhuman primate.

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2025-01-10 DOI:10.1016/j.nucmedbio.2025.108993

Yulong Xu, Yiming Xu, Frederick Andrew Bagdasarian, Tewodros Mulugeta Dagnew, Hua Cheng, Yanli Wang, Yongle Wang, Leyi Kang, Hsiao-Ying Wey, Can Zhang, Shijun Zhang, Changning Wang

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引用次数: 0

Abstract

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, [¹⁸F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [¹⁸F]CNL02, using nonhuman primate as a model system. In the brain of a rhesus macaque, [¹⁸F]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 [¹⁸F]CNL02 from the bloodstream. Metabolite analysis identified two predominant radiometabolites in the plasma. The regional brain time-activity curves (TACs) for [¹⁸F]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 [¹⁸F]CNL02 are imperative.

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非人类灵长类动物线粒体复合体I的新型PET放射配体的表征。

线粒体复合体I （MC-I）功能障碍的作用在一系列神经退行性疾病中得到了充分的证明。最近，一种新的正电子发射断层扫描（PET）放射性配体[18F]CNL02被合成用于靶向mc - 1。在本文中，我们提供了一个全面的表征[18F]CNL02，使用非人灵长类动物作为模型系统。在恒河猴的大脑中，[18F]CNL02在表达MC-I的区域表现出特异性结合。所有观察到的大脑区域都显示出快速的动力学特征。动脉血浆分析表明[18F]CNL02从血液中迅速清除。代谢物分析确定了血浆中两种主要的放射性代谢物。通过双组织室模型（2TCM）有效表征[18F]CNL02的区域脑时间活动曲线（TACs）。此外，采用Logan样地法可靠地估计了总分布体积。因此，继续发展和改进[18F]CNL02势在必行。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.