Fluorescently labeled therapeutic antibodies for detection of microscopic melanoma.

Fluorescently labeled therapeutic antibodies for detection of microscopic melanoma.
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DOI:
10.1002/lary.24102
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发表时间:
2013-11
期刊:
影响因子:
2.6
通讯作者:
Rosenthal, Eben L.
Rosenthal, Eben L.
中科院分区:
医学2区
文献类型:
--
作者:
Day, Kristine E.;Beck, Lauren N.;Deep, Nicholas L.;Kovar, Joy;Zinn, Kurt R.;Rosenthal, Eben L.

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Detection of microscopic disease during surgical resection of melanoma remains a significant challenge. To assess real-time optical imaging for visualization of microscopic cancer, we evaluated three FDA-approved therapeutic monoclonal antibodies. Prospective, basic science Melanoma cell lines (A375 and SKMEL5) were xenografted into the ears of immunodeficient mice. Bevacizumab, panitumumab, tocilizumab, or a non-specific IgG were covalently linked to a near-infrared (NIR) fluorescent probe (IRDye800CW) and systemically injected. Primary tumors were imaged and then resected under fluorescent guidance using the SPY, an NIR imaging system used in plastic and reconstructive surgeries to evaluate perfusion. Mice were also imaged with the Pearl Impulse small animal imager, an NIR imaging system designed for use with IRDye800CW. Post-resection, small tissue fragments were fluorescently imaged and presence of tumor subsequently confirmed by correlation with histology. All fluorescently-labeled therapeutic monoclonal antibodies could adequately delineate tumor from normal tissue based on tumor-to-background ratios (TBR) compared to IgG-IRDye800CW. On serial imaging, panitumumab achieved the highest TBRs with both SPY and Pearl (3.8 and 6.6). When used to guide resections, the antibody-dye conjugates generated TBRs in the range of 1.3-2.2 (average=1.6) using the SPY and 1.9-6.3 (average=2.7) using the Pearl. There was no significant difference amongst the antibodies with either imaging modality or cell line (one-way ANOVA). Our data suggests that FDA approved antibodies may be suitable targeting agents for the intraoperative fluorescent detection of melanoma. N/A
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