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

Molecular Imaging and Biology - Tập 17 - Trang 384-393 - 2014
Delphine L. Chen1,2, Jacquelyn T. Engle1, Elizabeth A. Griffin1, J. Philip Miller3, Wenhua Chu1, Dong Zhou1, Robert H. Mach1
1Division of Radiological Sciences and Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, USA
2Department of Internal Medicine, Washington University School of Medicine, St. Louis, USA
3Division of Biostatistics, Washington University School of Medicine, St. Louis, USA

Tóm tắt

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. [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. [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. [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.

Tài liệu tham khảo

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