Comparison of radiolabeled isatin analogs for imaging apoptosis with positron emission tomography

Nucl Med Biol. 2009 Aug;36(6):651-8. doi: 10.1016/j.nucmedbio.2009.03.008.


Introduction: Caspase-3 is one of the executioner caspases activated as a result of apoptosis. Radiolabeled isatins bind to caspase-3 with high affinity and are potential tracers for use with positron emission tomography to image apoptosis. We compared the ability of two novel radiolabeled isatins, [18F]WC-IV-3 and [11C]WC-98, to detect caspase-3 activation in a rat model of cycloheximide-induced liver injury.

Methods: Male Sprague-Dawley rats were treated with cycloheximide and then imaged with microPET 3 h later with [18F]WC-IV-3 and [11C]WC-98. Biodistribution studies were also performed simultaneously, with caspase-3 activation verified by fluorometric enzyme assay and Western blots.

Results: MicroPET imaging studies demonstrated similar behavior of both tracers but with a lower maximum peak with [11C]WC-98 than with [18F]WC-IV-3. Biodistribution studies demonstrated increased uptake of both tracers in the liver and spleen, but this was statistically significant only in the liver with both compounds. The level of [18F]WC-IV-3 uptake appeared to correlate roughly with rates of caspase-3 activation by the enzyme assay, but the magnitude of difference between treated and control groups was lower than that observed in previously published data with [18F]WC-II-89, another radiolabeled isatin analog. Activation was also confirmed in the liver and spleen but not in fat by Western blot.

Conclusion: [18F]WC-IV-3 uptake appears to correlate with increased caspase-3 enzyme activity, but the dynamic range of uptake of these two tracers appears to be less than that seen with [18F]WC-II-89. Studies are ongoing to verify these results in other animal models of apoptosis.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3 / metabolism
  • Caspase Inhibitors
  • Cycloheximide / pharmacology
  • Enzyme Activation
  • Isatin / chemistry*
  • Isatin / pharmacokinetics
  • Isatin / pharmacology
  • Isotope Labeling
  • Liver / diagnostic imaging
  • Liver / drug effects
  • Liver / injuries
  • Liver / pathology
  • Male
  • Positron-Emission Tomography
  • Pyrrolidines / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tissue Distribution


  • Caspase Inhibitors
  • Pyrrolidines
  • Isatin
  • Cycloheximide
  • Caspase 3
  • pyrrolidine