title: Narrow band imaging of squamous cell carcinoma tumors using topically delivered anti-EGFR antibody conjugated gold nanorods.
abstract: BACKGROUND
  Nanoparticles have recently gained interest as exogenous contrast agents in a variety of biomedical applications related to cancer detection and treatment. The objective of this study was to determine the potential of topically administered antibody conjugated gold nanorods (GNRs) for imaging squamous cell carcinomas (SCCs) of the skin using near-infrared narrowband imaging (NBI). Near-infrared (NIR) NBI images narrow wavelength bands to enhance contrast from plasmonic particles in a wide field portable and noncontact device that is clinically compatible for real-time tumor imaging and tumor margin demarcation.
  
  
  METHODS
  We conjugated GNRs to Cetuximab, a clinically approved humanized antibody that targets the epidermal growth factor receptor (EGFR), which is overexpressed on the surface of many tumor cells, especially SCCs. We excised subcutaneous xenografts of SCCs (A431) from Swiss nu/nu mice and divided the tumors into two groups: (1) the targeted group (Cetuximab conjugated GNRs) and (2) the control group (polyethylene glycol-conjugated GNRs). After topical application of particles and incubation for 30 minutes, the tumors were washed and imaged using NBI. In addition, we performed two-photon imaging to quantify the binding of EGFR targeted GNRs in tumors and their depth profile.
  
  
  RESULTS
  The NBI images showed a visual increase in contrast from tumors after topical administration of targeted GNR. Targeted GNR tumors showed increased contrast compared to tumors administered with the control GNR. There was a statistically significant increase in mean pixel intensity (∼2.5×) from targeted GNR tumors (n = 6). Two-photon microscopy images of targeted GNRs confirmed their binding affinity to the EGF receptors over expressed in the A431 tumors.
  
  
  CONCLUSIONS
  We have demonstrated that a topical application of gold nanorods targeted specifically to tumor growth factor receptors results in a significantly higher image contrast compared to nontargeted gold nanorods. These results demonstrate the feasibility of near-infrared NBI to image and demarcate tumor margins during surgical resection using topical administration of targeted GNR.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA. priyaveena@mail.utexas.edu
authors.forename: Priyaveena
authors.initials: P
authors.lastname: Puvanakrishnan
authors.forename: Parmeswaran
authors.initials: P
authors.lastname: Diagaradjane
authors.forename: S M Shams
authors.initials: SM
authors.lastname: Kazmi
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Dunn
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.forename: James W
authors.initials: JW
authors.lastname: Tunnell
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003287:Contrast Media / Q000008:administration & dosage; D066246:ErbB Receptors / Q000378:metabolism; D006046:Gold / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D058726:Nanoconjugates / Q000008:administration & dosage; D043942:Nanotubes; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D003287:Contrast Media; D058726:Nanoconjugates; D006046:Gold; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab