title: Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma.
abstract: Intraoperative, real-time fluorescence imaging may significantly improve tumor visualization and resection and postoperatively, in pathological assessment. To this end, we sought to determine the optimal FDA approved therapeutic monoclonal antibody for optical imaging of human cutaneous squamous cell carcinoma (cSCC). A near-infrared (NIR) fluorescent probe (IRDye800) was covalently linked to bevacizumab, panitumumab or tocilizumab and injected systemically into immunodeficient mice bearing either cutaneous tumor cell lines (SCC13) or cutaneous human tumor explants. Tumors were then imaged and resected under fluorescent guidance with the SPY, an FDA-approved intraoperative imaging system, and the Pearl Impulse small animal imaging system. All fluorescently labeled antibodies delineated normal tissue from tumor in SCC13 xenografts based on tumor-to-background (TBR) ratios. The conjugated antibodies produced TBRs of 1.2-2 using SPY and 1.6-3.6 using Pearl; in comparison, isotype control antibody IgG-IRDye produced TBRs of 1.0 (SPY) and 0.98 (Pearl). Comparison between antibodies revealed them to be roughly equivalent for imaging purposes with both the SPY and Pearl (p = 0.89 SPY, p = 0.99 Pearl; one way ANOVA). Human tumor explants were also imaged and tumor detection was highest with panitumumab-IRDye800 when using the SPY (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC.
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Day
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Beck
authors.forename: C Hope
authors.initials: CH
authors.lastname: Heath
authors.forename: Conway C
authors.initials: CC
authors.lastname: Huang
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D006801:Humans; D018796:Immunoconjugates; D007211:Indoles; D051379:Mice; D008856:Microscopy, Fluorescence; D061848:Optical Imaging / Q000379:methods; D012878:Skin Neoplasms / Q000175:diagnosis*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; C427728:IRDye800; D018796:Immunoconjugates; D007211:Indoles
keywords: animal model; antibody; cancer; cutaneous squamous cell carcinoma; fluorescence; optical imaging; surgery