Abstract

Copper-mediated radiofluorination (CMRF) of organoboronic precursors is the method of choice for late-stage radiofluorination of aromatic compounds as positron emission tomography (PET) radiotracers. However, CMRF generally requires harsh reaction conditions, a large amount of substrates, and harsh solvents (e.g., DMA) to proceed, affording variable radiochemical yields (RCYs). Using [18F]tosyl fluoride as the source of [18F]fluoride, we have found a highly efficient CMRF of organoboronic precursors, assisted by a directing group (DG) at the ortho position. The reaction can be carried out under mild conditions (even at room temperature) in acetonitrile and results in high RCYs, providing a novel strategy for the radiofluorination of aromatic compounds. The exploration of this strategy also provided more information about side reactions in CMRF. Using this strategy, [18F]olaparib has been radiosynthesized in high RCYs, with high molar activity and high chemical and radiochemical purities, demonstrating the great potential of DG-assisted CMRF in the preparation of 18F-labeled PET radiotracers.

Original languageEnglish
Pages (from-to)116-122
Number of pages7
JournalACS Medicinal Chemistry Letters
Volume15
Issue number1
DOIs
StatePublished - Jan 11 2024

Keywords

  • [F]olaparib
  • copper-mediated radiofluorination
  • directing group
  • fluorine-18
  • poly[ADP-ribose] polymerase 1
  • positron emission tomography

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