title: A Clinical Wide-Field Fluorescence Endoscopic Device for Molecular Imaging Demonstrating Cathepsin Protease Activity in Colon Cancer.
abstract: Early and effective detection of cancers of the gastrointestinal tract will require novel molecular probes and advances in instrumentation that can reveal functional changes in dysplastic and malignant tissues. Here, we describe adaptation of a wide-field clinical fiberscope to perform wide-field fluorescence imaging while preserving its white-light capability for the purpose of providing wide-field fluorescence imaging capability to point-of-care microscopes.
  
  
  
  We developed and used a fluorescent fiberscope to detect signals from a quenched probe, BMV109, that becomes fluorescent when cleaved by, and covalently bound to, active cathepsin proteases. Cathepsins are expressed in inflammation- and tumor-associated macrophages as well as directly from tumor cells and are a promising target for cancer imaging. The fiberscope has a 1-mm outer diameter enabling validation via endoscopic exams in mice, and therefore we evaluated topically applied BMV109 for the ability to detect colon polyps in an azoxymethane-induced colon tumor model in mice.
  
  
  
  This wide-field endoscopic imaging device revealed consistent and clear fluorescence signals from BMV109 that specifically localized to the polypoid regions as opposed to the normal adjacent colon tissue (p < 0.004) in the murine colon carcinoma model.
  
  
  
  The sensitivity of detection of BMV109 with the fluorescence fiberscope suggested utility of these tools for early detection at hard-to-reach sites. The fiberscope was designed to be used in conjunction with miniature, endoscope-compatible fluorescence microscopes for dual wide-field and microscopic cancer detection.
authors.affiliation: Department of Radiology, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.|Department of Pediatrics, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.|Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, 94305, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Sensarn
authors.affiliation: Department of Radiology, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.|Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, 94305, USA.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Zavaleta
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Ehud
authors.initials: E
authors.lastname: Segal
authors.affiliation: Department of Pediatrics, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rogalla
authors.affiliation: Department of Radiology, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.|Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Wansik
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Radiology, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA.|Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, 94305, USA.|Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.|Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bogyo
authors.affiliation: Department of Radiology, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA. ccontag@stanford.edu.|Department of Pediatrics, Stanford University, James H. Clark Center for Biomedical Engineering & Sciences, Stanford, CA, 94305, USA. ccontag@stanford.edu.|Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, 94305, USA. ccontag@stanford.edu.|Department of Microbiology & Immunology, Stanford University, Stanford, CA, 94305, USA. ccontag@stanford.edu.|Stanford University, 318 Campus Drive, Stanford, CA, 94305-5427, USA. ccontag@stanford.edu.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000378:metabolism*; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000473:pathology; D003111:Colonic Polyps / Q000473:pathology; D004724:Endoscopy / Q000295:instrumentation*; D005453:Fluorescence; D051379:Mice; D018613:Microscopy, Confocal; D057054:Molecular Imaging / Q000295:instrumentation*
chemical_list: D002403:Cathepsins
keywords: Biomedical optics; Endoscopy; Fiber optics; Fluorescence; Imaging systems; Medical imaging; Optical imaging; Optical probes