Imaging caspase-3 activation as a marker of apoptosis-targeted treatment response in cancer.
Imaging caspase-3 activation as a marker of apoptosis-targeted treatment response in cancer.
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DOI：
10.1007/s11307-014-0802-8
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发表时间：
2015-06
影响因子：
3.1
通讯作者：
Mach RH
中科院分区：
文献类型：
--
作者：
Chen DL;Engle JT;Griffin EA;Miller JP;Chu W;Zhou D;Mach RH
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.
