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 < 0.05). [(18)F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 enzyme activity. CONCLUSIONS: [(18)F]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.
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 < 0.05). [(18)F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 enzyme activity. CONCLUSIONS: [(18)F]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.
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