A fluoride-derived electrophilic late-stage fluorination reagent for PET imaging

Science. 2011 Nov 4;334(6056):639-42. doi: 10.1126/science.1212625.

Abstract

The unnatural isotope fluorine-18 ((18)F) is used as a positron emitter in molecular imaging. Currently, many potentially useful (18)F-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of (18)F requires rapid syntheses for which [(18)F]fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional [(18)F]fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic (18)F-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging.

Publication types

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

MeSH terms

  • Fluorides / chemistry
  • Fluorine Radioisotopes* / chemistry
  • Halogenation*
  • Indicators and Reagents
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Palladium / chemistry
  • Positron-Emission Tomography / methods*

Substances

  • Fluorine Radioisotopes
  • Indicators and Reagents
  • Organometallic Compounds
  • Palladium
  • Fluorides