One step radiosynthesis of 6-[(18)F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([(18)F]F-Py-TFP): a new prosthetic group for efficient labeling of biomolecules with fluorine-18

J Med Chem. 2010 Feb 25;53(4):1732-40. doi: 10.1021/jm9015813.


The labeling of biomolecules for positron emission tomography (PET) with no-carrier-added fluorine-18 is almost exclusively accomplished using prosthetic groups in a two step procedure. The inherent complexity of the process renders full automation a challenge and leads to protracted synthesis times. Here we describe a new (18)F-labeled prosthetic group based on nicotinic acid tetrafluorophenyl ester. Reaction of [(18)F]fluoride at 40 degrees C with the trimethylammonium precursor afforded 6-[(18)F]fluoronicotinic acid tetrafluorophenyl ester ([(18)F]F-Py-TFP) directly in 60-70% yield. [(18)F]F-Py-TFP was conveniently purified by Sep-Pak cartridge prior to incubation with a peptide containing the RGD sequence. The desired conjugate was formed rapidly and in good yields. An in vitro receptor-binding assay for the integrin alpha(v)beta(3) was established to explore competition with peptide and peptidomimetic prepared from F-Py-TFP with (125)I-echistatin. The nonradioactive conjugates were found to possess high binding affinities with calculated K(i) values in the low nanomolar range.

MeSH terms

  • Binding, Competitive
  • Cell Line, Tumor
  • Fluorine Radioisotopes
  • Humans
  • In Vitro Techniques
  • Integrin alphaVbeta3 / metabolism
  • Isotope Labeling
  • Nicotinic Acids / chemical synthesis*
  • Nicotinic Acids / chemistry
  • Nicotinic Acids / metabolism
  • Oligopeptides / chemistry
  • Radioligand Assay
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / metabolism


  • 6-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester
  • Fluorine Radioisotopes
  • Integrin alphaVbeta3
  • Nicotinic Acids
  • Oligopeptides
  • Radiopharmaceuticals
  • arginyl-glycyl-aspartic acid