Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography

J Med Chem. 2017 Sep 14;60(17):7350-7370. doi: 10.1021/acs.jmedchem.7b00632. Epub 2017 Jul 12.


Aggregates of tau and beta amyloid (Aβ) plaques constitute the histopathological hallmarks of Alzheimer's disease and are prominent targets for novel therapeutics as well as for biomarkers for diagnostic in vivo imaging. In recent years much attention has been devoted to the discovery and development of new PET tracers to image tau aggregates in the living human brain. Access to a selective PET tracer to image and quantify tau aggregates represents a unique tool to support the development of any novel therapeutic agent targeting pathological forms of tau. The objective of the study described herein was to identify such a novel radiotracer. As a result of this work, we discovered three novel PET tracers (2-(4-[11C]methoxyphenyl)imidazo[1,2-a]pyridin-7-amine 7 ([11C]RO6924963), N-[11C]methyl-2-(3-methylphenyl)imidazo[1,2-a]pyrimidin-7-amine 8 ([11C]RO6931643), and [18F]2-(6-fluoropyridin-3-yl)pyrrolo[2,3-b:4,5-c']dipyridine 9 ([18F]RO6958948)) with high affinity for tau neurofibrillary tangles, excellent selectivity against Aβ plaques, and appropriate pharmacokinetic and metabolic properties in mice and non-human primates.

Publication types

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

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Animals
  • Carbon Radioisotopes / chemistry*
  • Carbon Radioisotopes / pharmacokinetics
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / pharmacokinetics
  • Humans
  • Male
  • Mice
  • Papio
  • Positron-Emission Tomography / methods*
  • Protein Aggregation, Pathological / diagnostic imaging*
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacokinetics
  • tau Proteins / analysis*


  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Pyrimidines
  • tau Proteins