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

TitleIdentification of [F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging.
Publication TypeJournal Article
Year of Publication2018
AuthorsBernard-Gauthier V, Mossine AV, Mahringer A, Aliaga A, Bailey JJ, Shao X, Stauff J, Arteaga J, Sherman P, Grand'Maison M, Rochon P-L, Wängler B, Wängler C, Bartenstein P, Kostikov A, Kaplan DR, Fricker G, Rosa-Neto P, Scott PJH, Schirrmacher R
JournalJ Med Chem
Volume61
Issue4
Pagination1737-1743
Date Published2018 Feb 22
ISSN1520-4804
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 F-labeled optimized lead suitable for in vivo imaging of Trk, [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.

DOI10.1021/acs.jmedchem.7b01607
Alternate JournalJ. Med. Chem.
PubMed ID29257860

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