Development of the First Potential Nonpeptidic Positron Emission Tomography Tracer for the Imaging of CCR2 Receptors

ChemMedChem. 2021 Feb 17;16(4):640-645. doi: 10.1002/cmdc.202000728. Epub 2020 Nov 23.

Abstract

Herein we report the design and synthesis of a series of highly selective CCR2 antagonists as 18 F-labeled PET tracers. The derivatives were evaluated extensively for their off-target profile at 48 different targets. The most potent and selective candidate was applied in vivo in a biodistribution study, demonstrating a promising profile for further preclinical development. This compound represents the first potential nonpeptidic PET tracer for the imaging of CCR2 receptors.

Keywords: CCR2; CCR5 antagonists; PET; TAK-779; chemokine receptors; molecular imaging; radiolabeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Development*
  • Humans
  • Molecular Structure
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacology*
  • Receptors, CCR2 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • CCR2 protein, human
  • Radiopharmaceuticals
  • Receptors, CCR2