Sulfur [18F]Fluoride Exchange Click Chemistry Enabled Ultrafast Late-Stage Radiosynthesis

J Am Chem Soc. 2021 Mar 17;143(10):3753-3763. doi: 10.1021/jacs.0c09306. Epub 2021 Feb 25.

Abstract

The lack of efficient [18F]fluorination processes and target-specific organofluorine chemotypes remains the major challenge of fluorine-18 positron emission tomography (PET). We report here an ultrafast isotopic exchange method for the radiosynthesis of novel PET agent aryl [18F]fluorosulfate enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully automated 18F-radiolabeling of 25 structurally and functionally diverse aryl fluorosulfates with excellent radiochemical yield (83-100%, median 98%) and high molar activity (280 GBq μmol-1) at room temperature in 30 s. The purification of radiotracers requires no time-consuming HPLC but rather a simple cartridge filtration. We further demonstrate the imaging application of a rationally designed poly(ADP-ribose) polymerase 1 (PARP1)-targeting aryl [18F]fluorosulfate by probing subcutaneous tumors in vivo.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Click Chemistry*
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry
  • Contrast Media / metabolism
  • Density Functional Theory
  • Drug Stability
  • Fluorides / chemical synthesis
  • Fluorides / chemistry*
  • Fluorides / metabolism
  • Fluorine Radioisotopes / chemistry
  • Humans
  • Mice
  • Neoplasms / diagnostic imaging
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / metabolism
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / metabolism
  • Sulfur Compounds / chemical synthesis
  • Sulfur Compounds / chemistry*
  • Sulfur Compounds / metabolism
  • Transplantation, Heterologous

Substances

  • Contrast Media
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Sulfur Compounds
  • sulfur fluoride
  • Poly(ADP-ribose) Polymerases
  • Fluorine-18
  • Fluorides