Synthesis of high-molar-activity [18F]6-fluoro-L-DOPA suitable for human use via Cu-mediated fluorination of a BPin precursor

Nat Protoc. 2020 May;15(5):1742-1759. doi: 10.1038/s41596-020-0305-9. Epub 2020 Apr 8.

Abstract

[18F]6-fluoro-L-DOPA ([18F]FDOPA) is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that is used to image Parkinson's disease, brain tumors, and focal hyperinsulinism of infancy. Despite these important applications, [18F]FDOPA PET remains underutilized because of synthetic challenges associated with accessing the radiotracer for clinical use; these stem from the need to radiofluorinate a highly electron-rich catechol ring in the presence of an amino acid. To address this longstanding challenge in the PET radiochemistry community, we have developed a one-pot, two-step synthesis of high-molar-activity [18F]FDOPA by Cu-mediated fluorination of a pinacol boronate (BPin) precursor. The method is fully automated, has been validated to work well at two separate sites (an academic facility with a cyclotron on site and an industry lab purchasing [18F]fluoride from an outside vendor), and provides [18F]FDOPA in reasonable radiochemical yield (2.44 ± 0.70 GBq, 66 ± 19 mCi, 5 ± 1%), excellent radiochemical purity (>98%) and high molar activity (76 ± 30 TBq/mmol, 2,050 ± 804 Ci/mmol), n = 26. Herein we report a detailed protocol for the synthesis of [18F]FDOPA that has been successfully implemented at two sites and validated for production of the radiotracer for human use.

Publication types

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

MeSH terms

  • Boronic Acids / chemistry*
  • Chemistry Techniques, Synthetic / methods*
  • Copper / chemistry*
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Dihydroxyphenylalanine / chemical synthesis
  • Fluorine Radioisotopes
  • Glycols / chemistry*
  • Halogenation

Substances

  • Boronic Acids
  • Fluorine Radioisotopes
  • Glycols
  • pinacol
  • fluorodopa F 18
  • Dihydroxyphenylalanine
  • Copper