title: EGFR Overexpressed in Colonic Neoplasia Can be Detected on Wide-Field Endoscopic Imaging.
abstract: OBJECTIVE
  Colorectal cancer initially lies dormant as dysplasia, a premalignant state that provides an opportunity for early cancer detection. Dysplasia can be flat in morphology, focal in size, and patchy in distribution, and thus it appears "invisible" on conventional wide-field endoscopy.
  
  
  OBJECTIVE
  We aim to develop and validate a peptide that is specific for epidermal growth factor receptor (EGFR), a cell surface target that is overexpressed in colonic adenomas and is readily accessible for imaging.
  
  
  METHODS
  We expressed and purified the extracellular domain of EGFR for use with phage display to identify a peptide QRHKPRE that binds to domain 2 of this target. A near-infrared fluorescence endoscope was used to perform in vivo imaging to validate specific peptide binding to spontaneous colonic adenomas in a mouse model with topical administration. We also validated specific peptide binding to human colonic adenomas on immunohistochemistry and immunofluorescence.
  
  
  RESULTS
  After labeling with Cy5.5, we validated specific peptide binding to EGFR on knockdown and competition studies. Peptide binding to cells occurred within 2.46 min and had an affinity of 50 nm. No downstream signaling was observed. We measured a target-to-background ratio of 4.0±1.7 and 2.7±0.7, for polyps and flat lesions, respectively. On immunofluorescence of human colonic specimens, greater intensity from peptide binding to dysplasia than normal was found with a 19.4-fold difference.
  
  
  CONCLUSIONS
  We have selected and validated a peptide that can be used as a specific contrast agent to identify colonic adenomas that overexpress EGFR in vivo on fluorescence endoscopy.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: Joshi
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Xiyu
authors.initials: X
authors.lastname: Duan
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Pant
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Owens
authors.affiliation: 1] Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA [2] Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA [3] Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Wang