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J Med Chem. 2018 Feb 22;61(4):1737-1743. doi: 10.1021/acs.jmedchem.7b01607. Epub 2018 Jan 5.

Identification of [18F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging.

Author information

1
Department of Oncology, Division of Oncological Imaging, University of Alberta , Edmonton, AB T6G 2R3, Canada.
2
Department of Radiology, Division of Nuclear Medicine, The University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.
3
Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg , Heidelberg 69120, Germany.
4
Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, Douglas Mental Health University Institute , Montreal, QC H4H 1R3, Canada.
5
Biospective Inc. , Montreal, QC H4P 2R2, Canada.
6
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University , Montreal, QC H3A 2B4, Canada.
7
Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich , Munich 81377, Germany.
8
Program in Neurosciences and Mental Health, Hospital for Sick Children , Toronto, ON M5G 0A4, Canada.
9
The Interdepartmental Program in Medicinal Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.

Abstract

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 18F-labeled optimized lead suitable for in vivo imaging of Trk, [18F]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.

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