Characterizing breast cancer xenograft epidermal growth factor receptor expression by using near-infrared optical imaging.
Characterizing breast cancer xenograft epidermal growth factor receptor expression by using near-infrared optical imaging.
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DOI:
10.3109/02841850903008800
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发表时间:
2009-12
期刊:
影响因子:
--
通讯作者:
Chen X
中科院分区:
文献类型:
--
作者:
Wang K;Wang K;Li W;Huang T;Li R;Wang D;Shen B;Chen X
Epidermal growth factor receptor (EGFR) overexpression is associated with several key features of cancer development and growth. Therefore, EGFR is a very promising biological target for tumor diagnosis and anticancer therapy. Characterization of EGFR expression is important for clinicians to select patients for EGFR-targeted therapy and evaluate therapeutic effects. To investigate whether near-infrared (NIR) fluorescent dye Cy5.5-labeled anti-EGFR monoclonal antibody Erbitux can characterize EGFR expression level in MDA-MB-231 and MCF-7 breast cancer xenografts using an in vivo NIR imaging method. A fluorochrome probe was designed by coupling Cy5.5 to Erbitux through acidylation, and the fluorescence property of the Erbitux-Cy5.5 conjugate was characterized by fluorospectroscopy. Flow cytometry and laser confocal microscopy were used to test the EGFR specificity of the antibody probe in vitro. Erbitux-Cy5.5 was also injected intravenously into immune-deficient mice bearing MDA-MB-231 or MCF-7 tumors. Whole-body and region-of-interest fluorescence images were acquired and analyzed. The EGFR expression was also analyzed and confirmed by immunohistochemical assay. The maximum excitation/emission wavelength for the Erbitux-Cy5.5 probe was 674/697 nm, similar to that of free Cy5.5 (674/712 nm). Confocal microscopy confirmed receptor-specific uptake in MDA-MB-231 and MCF-7 cells. In flow cytometry probe specificity assay, Erbitux-Cy5.5 showed a 9.32-fold higher affinity for MDA-MB-231 than MCF-7 cells. In vivo NIR imaging also indicated specific uptake in EGFR-positive tumors. Probe uptake rate and maximum intake dose in MDA-MB-231 were significantly higher than those in MCF-7 xenografts (P < 0.001). Immunohistochemical staining confirmed the in vivo imaging results, showing differentiated EGFR expression in MDA-MB-231 (+ + +) and MCF-7 (+) tumor tissues. Erbitux-Cy5.5 may be used as a specific NIR contrast agent for the noninvasive characterization of EGFR expression level in breast cancer xenografts.
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影响因子:
11.2
作者:
Veiseh, Mandana;Gabikian, Patrik;Olson, James M.
通讯作者:
Olson, James M.
影响因子:
11.5
作者:
Kaijzel, Eric L.;van der Pluijm, Gabri;Lowik, Clemens W. G. M.
通讯作者:
Lowik, Clemens W. G. M.
影响因子:
11.2
作者:
Chen, XY;Conti, PS;Moats, RA
通讯作者:
Moats, RA
影响因子:
78.5
作者:
Chabner, BA;Roberts, TG
通讯作者:
Roberts, TG
影响因子:
19.7
作者:
Gee, Michael S.;Upadhyay, Rabi;Mahmood, Umar
通讯作者:
Mahmood, Umar