Stereomicroscopic fluorescence imaging of head and neck cancer xenografts targeting CD147.

ABSTRACT

PURPOSE: To demonstrate that systemically administered fluorescently labeled anti-CD147 antibody can detect head and neck squamous cell carcinoma xenografts in vivo. EXPERIMENTAL DESIGN: In vivo immunodeficient murine model. RESULTS: Peak tumor fluorescence was visualized by near infrared stereomicroscopy in SCC-1 tumors at 24 hours after systemic injection of anti-CD147Cy5.5 bioconjugate. SCC-1 xenografts demonstrated significantly higher fluorescent intensity after administration of CD147Cy5.5 (48 au, p < 0.0001) compared to IgG1kCy5.5 isotype control antibody (9 au). FaDu tumors overexpressing CD147 (FaDu/E) demonstrated higher fluorescence (53 au) compared to control vector transfected cells (FaDu, 33 au, p < 0.0001) which was higher than CD147 knockdown cells (FaDu/siE, 5 au, p < 0.0001). METHODS: To determine if fluorescently labeled anti-CD147 antibody was specific for tumors in vivo, anti-CD147 and non-specific IgG1k antibody were labeled with a near infrared fluorophore (Cy5.5) and administered systemically to immunodeficient mice bearing SCC-1 xenografts. Imaging was performed over a 72 hour period using brightfield and fluorescent (685-735 nm) stereomicroscopy. To determine if fluorescence varied with receptor expression, SCID mice were xenografted with cell lines expressing variable amounts of CD147 FaDu (control vector transfected), FaDu/siE (siRNA CD147 knockdown) or FaDu/E (CD147 overexpressing) cells. CONCLUSIONS: This data suggests fluorescently labeled anti-CD147 may have clinical utility in detection of HNSCC.