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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Drug Design
  • Fluorine Radioisotopes*
  • Humans
  • Neoplasms / diagnostic imaging
  • Neurodegenerative Diseases / diagnostic imaging
  • Positron-Emission Tomography / methods*
  • Protein Kinase Inhibitors
  • Receptor, trkA / antagonists & inhibitors*

Substances

  • Fluorine Radioisotopes
  • Protein Kinase Inhibitors
  • Receptor, trkA
  • Fluorine-18