In Vitro and In Vivo Evaluation of the Caspase-3 Substrate-Based Radiotracer [18F]-CP18 for PET Imaging of Apoptosis in Tumors
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A novel caspase-3 substrate-based probe [18F]-CP18 was evaluated as an in vivo positron emission tomography (PET) imaging agent for monitoring apoptosis in tumors.
Uptake of [18F]-CP18 in cell assays and tumors was measured. Caspase-3/7 activities in cell lysates and tumor homogenates were determined. Autoradiography,Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and cleaved caspase-3 immunostaining were performed on adjacent tumor sections to identify areas of apoptosis.
The in vitro cell assays showed caspase-3-dependent uptake of [18F]-CP18 in tumor cells when treated with an apoptosis inducer. The in vivo microPET imaging signal of [18F]-CP18 in xenograft tumors correlated with the ex vivo caspase-3/7 activities in these tumors. Furthermore, tumor autoradiographies of [18F]-CP18 in tumor sections matched adjacent sections stained by TUNEL and caspase-3 immunohistochemistry (IHC).
[18F]-CP18 demonstrated high affinity and selectivity for activated caspase-3 both in vitro and in vivo, and the results support [18F]-CP18 as a promising new PET imaging agent for apoptosis.
Key words[18F]-CP18 Caspase-3 PET imaging Apoptosis Caspase imaging
Conflict of Interest
The authors declare that they have no conflict of interest.
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