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

Autor: Bernard-Gauthier V; Department of Oncology, Division of Oncological Imaging, University of Alberta , Edmonton, AB T6G 2R3, Canada., Mossine AV; Department of Radiology, Division of Nuclear Medicine, The University of Michigan Medical School , Ann Arbor, Michigan 48109, United States., Mahringer A; Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg , Heidelberg 69120, Germany., Aliaga A; Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, Douglas Mental Health University Institute , Montreal, QC H4H 1R3, Canada., Bailey JJ; Department of Oncology, Division of Oncological Imaging, University of Alberta , Edmonton, AB T6G 2R3, Canada., Shao X; Department of Radiology, Division of Nuclear Medicine, The University of Michigan Medical School , Ann Arbor, Michigan 48109, United States., Stauff J; Department of Radiology, Division of Nuclear Medicine, The University of Michigan Medical School , Ann Arbor, Michigan 48109, United States., Arteaga J; Department of Radiology, Division of Nuclear Medicine, The University of Michigan Medical School , Ann Arbor, Michigan 48109, United States., Sherman P; Department of Radiology, Division of Nuclear Medicine, The University of Michigan Medical School , Ann Arbor, Michigan 48109, United States., Grand'Maison M; Biospective Inc. , Montreal, QC H4P 2R2, Canada., Rochon PL; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University , Montreal, QC H3A 2B4, Canada., Wängler B, Wängler C, Bartenstein P; Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich , Munich 81377, Germany., Kostikov A; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University , Montreal, QC H3A 2B4, Canada., Kaplan DR; Program in Neurosciences and Mental Health, Hospital for Sick Children , Toronto, ON M5G 0A4, Canada., Fricker G; Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg , Heidelberg 69120, Germany., Rosa-Neto P; Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, Douglas Mental Health University Institute , Montreal, QC H4H 1R3, Canada., Scott PJH; Department of Radiology, Division of Nuclear Medicine, The University of Michigan Medical School , Ann Arbor, Michigan 48109, United States.; The Interdepartmental Program in Medicinal Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States., Schirrmacher R; Department of Oncology, Division of Oncological Imaging, University of Alberta , Edmonton, AB T6G 2R3, Canada.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2018 Feb 22; Vol. 61 (4), pp. 1737-1743. Date of Electronic Publication: 2018 Jan 05.
DOI: 10.1021/acs.jmedchem.7b01607
Abstrakt: 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 18 F-labeled optimized lead suitable for in vivo imaging of Trk, [ 18 F]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.
Databáze: MEDLINE