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

Delphine L. Chen, Dong Zhou, Wenhua Chu, Phillip E. Herrbrich, Lynne A. Jones, Justin M. Rothfuss, Jacquelyn T. Engle, Marco Geraci, Michael J. Welch, Robert H. Mach

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33 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)651-658
Number of pages8
JournalNuclear Medicine and Biology
Volume36
Issue number6
DOIs
StatePublished - Aug 1 2009

Keywords

  • Apoptosis
  • Caspase-3
  • Liver injury
  • Positron emission tomography
  • Radiolabeled isatins

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    Chen, D. L., Zhou, D., Chu, W., Herrbrich, P. E., Jones, L. A., Rothfuss, J. M., Engle, J. T., Geraci, M., Welch, M. J., & Mach, R. H. (2009). Comparison of radiolabeled isatin analogs for imaging apoptosis with positron emission tomography. Nuclear Medicine and Biology, 36(6), 651-658. https://doi.org/10.1016/j.nucmedbio.2009.03.008