Identification of [18F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging
Identification of [18F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging
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DOI：
10.1021/acs.jmedchem.7b01607
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发表时间：
2018-02-22
影响因子：
7.3
通讯作者：
Schirrmacher, Ralf
中科院分区：
文献类型：
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作者：
Bernard-Gauthier, Vadim;Mossine, Andrew V.;Schirrmacher, Ralf
在神经系统疾病和癌症中发现TrkA/B/C受体和致癌Trk融合蛋白的表达和功能失调信号传导的变化。在这里，我们描述了第一个F-18标记的优化铅的发展，适合于在体内成像的Trk，[F-18]TRACK，这是放射性合成容易从非活化的芳基前体，同时大大减少P-gp的责任和改善脑动力学相比，以前的铅，同时显示高的靶亲和力和人类激酶组选择性。
Changes in expression and dysfunctional signaling of TrkA/B/C receptors and oncogenic Trk fusion proteins are found in neurological diseases and cancers. Here, we describe the development of a first F-18-labeled optimized lead suitable for in vivo imaging of Trk, [F-18]TRACK, which is radiosynthesized with ease from a nonactivated aryl precursor concurrently combining largely reduced P-gp liability and improved brain kinetics compared to previous leads while displaying high on-target affinity and human kinome selectivity.