Discovery of 6-(Fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18)F]-MK-6240): A Positron Emission Tomography (PET) Imaging Agent for Quantification of Neurofibrillary Tangles (NFTs)

J Med Chem. 2016 May 26;59(10):4778-89. doi: 10.1021/acs.jmedchem.6b00166. Epub 2016 May 5.


Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery of new disease modifying therapeutics targeting tau pathology. Herein, we present the discovery of 6-(fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine, 6 ([(18)F]-MK-6240), as a novel PET tracer for detecting NFTs. 6 exhibits high specificity and selectivity for binding to NFTs, with suitable physicochemical properties and in vivo pharmacokinetics.

MeSH terms

  • Drug Discovery*
  • Fluorine Radioisotopes / chemistry
  • Humans
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry*
  • Isoquinolines / pharmacokinetics
  • Molecular Imaging*
  • Molecular Structure
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology*
  • Positron-Emission Tomography*


  • Fluorine Radioisotopes
  • Isoquinolines
  • MK-6240