期刊
CANCER RESEARCH
卷 67, 期 8, 页码 3809-3817出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-06-3794
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资金
- Intramural NIH HHS Funding Source: Medline
Optical probes that yield high target-to-background ratios are necessary to detect microfoci of cancer that would otherwise escape detection with white light imaging. Target-specific activation of the optical signal at tumor foci is one mechanism by which high target and low background signal can be achieved. Here, we describe a two-step activation process in which the tumors are first pretargeted with a nonfluorescent biotinylated monoclonal antibody [cetuximab (Erbitux) targeting human epidermal growth factor receptor type 1 (HERI)]. Following this, a second agent, neutravidin-BODIPY-FL fluorescent conjugate, is given and binds to the previously targeted antibody, resulting in an similar to 10-fold amplification of the optical fluorescence signal, leading to high tumor-to-background ratios. Spectral fluorescence imaging was done in a mouse model of peritoneal metastasis using a HER1-overexpressing cell line (A431) after pretargeting with biotinylated cetuximab and 3 h after administration of neutravidin-conjugated BODIPY-FL. Both aggregated tumors as well as small cancer implants were clearly visualized in vivo. For lesions similar to 0.8 mm or greater in diameter, the spectral fluorescence imaging had a sensitivity of 96% (178 of 185) and a specificity of 98% (188 of 191). This two-step activation paradigm (pretargeting followed by neutravidinbiotin binding with an attached activatable fluorophore) could be useful in tumor-specific molecular imaging of various targets to guide surgical resections.
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