Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5041-6. doi: 10.1016/j.bmcl.2006.07.045. Epub 2006 Aug 7.


A non-peptide-based isatin sulfonamide analog, WC-II-89, was synthesized and its inhibition toward recombinant human caspase-3 and other caspases was determined. This compound showed high potency for inhibiting caspase-3 and -7, and high selectivity against caspases-1, -6, and -8. [(18)F]WC-II-89 was synthesized via a nucleophilic substitution of the corresponding mesylate precursor in high yield and radiochemical purity. Biodistribution studies using [(18)F]WC-II-89 revealed higher uptake in liver and spleen of cycloheximide-treated rats, an animal model of apoptosis, relative to control animals. Western blot analysis confirmed the presence of activated caspase-3 in the liver and spleen of cycloheximide-treated animals. MicroPET imaging studies revealed a high uptake of the radiotracer in the liver of a cycloheximide-treated rat relative to the untreated control. These data suggest that [(18)F]WC-II-89 is a potential radiotracer for imaging caspase-3 activation in tissues undergoing apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3
  • Caspase 7
  • Caspase Inhibitors
  • Caspases / analysis
  • Caspases / metabolism*
  • Fluorine Radioisotopes* / pharmacokinetics
  • Isatin / analogs & derivatives*
  • Isatin / chemical synthesis
  • Isatin / pharmacokinetics
  • Liver / metabolism
  • Positron-Emission Tomography
  • Radionuclide Imaging / methods
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Recombinant Proteins
  • Spleen / metabolism
  • Sulfonamides
  • Tissue Distribution


  • Caspase Inhibitors
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Recombinant Proteins
  • Sulfonamides
  • Isatin
  • CASP3 protein, human
  • CASP7 protein, human
  • Casp3 protein, rat
  • Caspase 3
  • Caspase 7
  • Caspases