Stereomicroscopic fluorescence imaging of head and neck cancer xenografts targeting CD147.
OBJECTIVE
To demonstrate that systemically administered fluorescently labeled anti-CD147 antibody can detect head and neck squamous cell carcinoma xenografts in vivo.


METHODS
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-CD147:Cy5.5 bioconjugate. SCC-1 xenografts demonstrated significantly higher fluorescent intensity after administration of CD147:Cy5.5 (48 au, p < 0.0001) compared to IgG1k:Cy5.5 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.
Newman
J Robert
JR
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0012, USA.
Gleysteen
John P
JP
Barañano
Christopher F
CF
Bremser
Jennifer R
JR
Zhang
Wenyue
W
Zinn
Kurt R
KR
Rosenthal
Eben L
EL
D000818:Animals; D051926:Basigin / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D004867:Equipment Design; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D051379:Mice; D016513:Mice, SCID; D008853:Microscopy / Q000379:methods; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods*; D008856:Microscopy, Fluorescence / Q000295:instrumentation / Q000379:methods*; D009368:Neoplasm Transplantation; D012867:Skin / Q000378:metabolism
D003287:Contrast Media; D007074:Immunoglobulin G; D051926:Basigin