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Imaging caspase-3 activation as a marker of apoptosis-targeted treatment response in cancer.


ABSTRACT: PURPOSE:We tested whether positron emission tomography (PET) with the caspase-3-targeted isatin analog [(18)F]WC-4-116 could image caspase-3 activation in response to an apoptosis-inducing anticancer therapy. PROCEDURES:[(18)F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. Biodistribution studies with [(18)F]WC-4-116 and [(18)F]ICMT-18, a non-caspase-3-targeted tracer, as well as [(18)F]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. RESULTS:[(18)F]WC-4-116 increased 8?±?2 fold in etoposide-treated cells. The [(18)F]WC-4-116 % ID/g also increased significantly in tumors with high caspase-3 enzyme activity (p?

SUBMITTER: Chen DL 

PROVIDER: S-EPMC4874215 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Imaging caspase-3 activation as a marker of apoptosis-targeted treatment response in cancer.

Chen Delphine L DL   Engle Jacquelyn T JT   Griffin Elizabeth A EA   Miller J Philip JP   Chu Wenhua W   Zhou Dong D   Mach Robert H RH  

Molecular imaging and biology 20150601 3


<h4>Purpose</h4>We tested whether positron emission tomography (PET) with the caspase-3-targeted isatin analog [(18)F]WC-4-116 could image caspase-3 activation in response to an apoptosis-inducing anticancer therapy.<h4>Procedures</h4>[(18)F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. Biodistribution studies with [(18)F]WC-4-116 and [(18)F]ICMT-18, a non-caspase-3-targeted tracer, as well as [(18)F]WC-4-116 microPET imaging assessed responses in Colo205 tumor-bearing mice trea  ...[more]

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