Imaging Caspase-3 Activation as a Marker of Apoptosis-Targeted Treatment Response in Cancer

Delphine L. Chen, Jacquelyn T. Engle, Elizabeth A. Griffin, J. Philip Miller, Wenhua Chu, Dong Zhou, Robert H. Mach

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Results: [18F]WC-4-116 increased 8 ± 2 fold in etoposide-treated cells. The [18F]WC-4-116 % ID/g also increased significantly in tumors with high caspase-3 enzyme activity (p < 0.05). [18F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 enzyme activity.

Purpose: We tested whether positron emission tomography (PET) with the caspase-3-targeted isatin analog [18F]WC-4-116 could image caspase-3 activation in response to an apoptosis-inducing anticancer therapy.

Procedures: [18F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. Biodistribution studies with [18F]WC-4-116 and [18F]ICMT-18, a non-caspase-3-targeted tracer, as well as [18F]WC-4-116 microPET imaging assessed responses in Colo205 tumor-bearing mice treated with death receptor 5 (DR5)-targeted agonist antibodies. Immunohistochemical staining and enzyme assays confirmed caspase-3 activation. Two-way analysis of variance or Student’s t test assessed for treatment-related changes in tracer uptake.

Conclusions: [18F]WC-4-116 uptake in vivo reflects increased caspase-3 activation and may be useful for detecting caspase-3-mediated apoptosis treatment responses in cancer.

Original languageEnglish
Pages (from-to)384-393
Number of pages10
JournalMolecular Imaging and Biology
Volume17
Issue number3
DOIs
StatePublished - Jun 1 2015

Keywords

  • Apoptosis
  • Cancer
  • Caspase-3
  • Positron emission tomography

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