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Research Articles: Therapeutics, Targets, and Development

Use of fluorescent labeled anti–epidermal growth factor receptor antibody to image head and neck squamous cell carcinoma xenografts

¹ Division of Otolaryngology-Head and Neck Surgery, Department of Surgery and ² Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

Requests for reprints: Eben L. Rosenthal, Division of Otolaryngology, Department of Surgery, University of Alabama at Birmingham, BDB Suite 563, 1808 7th Avenue South, Birmingham, AL 35294-0012. Phone: 205-934-9767; Fax: 205-934-3993. E-mail: oto{at}uab.edu

Abstract

Physicians and surgeons rely on subtle tissue changes to detect the extent of tumors and the presence of residual disease in the clinical setting. The development of a cancer-specific fluorescent contrast agent has the potential to provide real-time tumor imaging in the clinic or operating room. Because epidermal growth factor receptor (EGFR) is highly overexpressed on the surface of head and neck squamous cell carcinoma (HNSCC), we sought to determine if fluorescently labeled anti-EGFR antibody could be used to image HNSCC xenografts in vivo. Cetuximab or control isotype-matched IgG1 was conjugated with the Cy5.5 fluorochrome and systemically injected into mice bearing human split thickness skin grafts, tumor cell line xenografts, transplanted human tumor xenografts, or mouse mesothelioma tumors. Xenografts were imaged by time-domain fluorescence imaging or fluorescence stereomicroscopy. Both imaging modalities detected specific uptake of cetuximab-Cy5.5 in HNSCC xenografts with significantly higher fluorescence levels relative to control IgG1-Cy5.5. Tumor xenograft fluorescence was higher compared with background (before injection), human split thickness skin grafts, or mouse mesothelioma tumors at 24, 48, and 72 h. Fluorescence was detected in multiple HNSCC tumor cell lines with variable EGFR expression levels. Mock resections of flank tumors using fluorescence stereomicroscopy showed that small (2 mm) specimens could be detected in the surgical wound bed. These results show the feasibility of using fluorescently labeled anti-EGFR antibody to detect human tumors in the surgical setting. [Mol Cancer Ther 2007;6(4):1230–8]

Grant support: American Cancer Society grant RSG-06-1006-01-CCE (E.L. Rosenthal) and the University of Alabama at Birmingham Comprehensive Cancer Center core grant NIH, P30 CA13148.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

³ http://rsb.info.nih.gov/ij/

Received 11/30/06; accepted 2/ 9/07.

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