First-in-Human Brain Imaging of [18F]TRACK, a PET tracer for Tropomyosin Receptor Kinases

ACS Chem Neurosci. 2019 Jun 19;10(6):2697-2702. doi: 10.1021/acschemneuro.9b00144. Epub 2019 Apr 29.


The tropomyosin receptor kinase TrkA/B/C family is responsible for human neuronal growth, survival, and differentiation from early nervous system development stages onward. Downregulation of TrkA/B/C receptors characterizes numerous neurological disorders including Alzheimer's disease (AD). Abnormally expressed Trk receptors or chimeric Trk fusion proteins are also well-characterized oncogenic drivers in a variety of neurogenic and non-neurogenic human neoplasms and are currently the focus of intensive clinical research. Previously, we have described the clinical translation of a highly selective and potent carbon-11-labeled pan-Trk radioligand and the preclinical characterization of the optimized fluorine-18-labeled analogue, [18F]TRACK, for in vivo Trk positron emission tomography (PET) imaging. We describe herein central nervous system selectivity assessment and first-in-human study of [18F]TRACK.

Keywords: PET; Trk; Tropomyosin receptor kinase; copper-mediated radiofluorination; fluorine-18; kinase inhibitor; neuroimaging; positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Fluorine Radioisotopes / pharmacokinetics*
  • Humans
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / metabolism
  • Mice
  • Neuroimaging / methods*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptor Protein-Tyrosine Kinases / analysis*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, trkA / analysis
  • Receptor, trkA / metabolism
  • Receptor, trkB / analysis
  • Receptor, trkB / metabolism
  • Receptor, trkC / analysis
  • Receptor, trkC / metabolism


  • Fluorine Radioisotopes
  • Membrane Glycoproteins
  • NTRK1 protein, human
  • Radiopharmaceuticals
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Receptor, trkB
  • Receptor, trkC
  • tropomyosin-related kinase-B, human