(R)-[F]NEBIFQUINIDE：一种有前途的新型 TSPO 成像 PET 示踪剂。
(R)-[F]NEBIFQUINIDE: A promising new PET tracer for TSPO imaging.
机构信息
Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 42, 1090, Vienna, Austria.
Institute of Organic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
出版信息
Eur J Med Chem. 2019 Aug 15;176:410-418. doi: 10.1016/j.ejmech.2019.05.008. Epub 2019 May 10.
Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO), has a high diagnostic potential in neurodegenerative disorders and cancer. However, TSPO is considered a challenge for molecular imaging due to the poor availability of suitable radiotracers with adequate pharmacokinetic properties. Here, we describe the development of a radiofluorinated pyridinyl isoquinoline analogue of the established TSPO PET tracer (R)-[C]PK11195 with improved binding properties in all known human TSPO phenotypes. We conducted a complete preclinical evaluation using in vitro, in vivo and ex vivo methods to assess the performance of this novel radiotracer and observed high specific binding of the radiotracer to TSPO, as well as high metabolic stability. Therefore, we propose this radiolabeled compound for further evaluation in animal models as well as in clinical trials.
正电子发射断层扫描（PET）成像的 18 kDa 转位蛋白（TSPO），在神经退行性疾病和癌症中有很高的诊断潜力。然而，由于缺乏具有适当药代动力学特性的合适放射性示踪剂，TSPO 被认为是分子成像的一个挑战。在这里，我们描述了一种放射性氟化吡啶基异喹啉类似物的开发，这是一种已建立的 TSPO PET 示踪剂（R）-[C]PK11195，在所有已知的人类 TSPO 表型中具有改善的结合特性。我们使用体外、体内和离体方法进行了全面的临床前评估，以评估这种新型放射性示踪剂的性能，并观察到放射性示踪剂与 TSPO 的高特异性结合，以及高代谢稳定性。因此，我们建议将这种放射性标记化合物进一步在动物模型和临床试验中进行评估。
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