title: In vivo molecular mapping of the tumor microenvironment in an azoxymethane-treated mouse model of colon carcinogenesis.
abstract: OBJECTIVE
  Development of miniaturized imaging systems with molecular probes enables examination of molecular changes leading to initiation and progression of colorectal cancer in an azoxymethane (AOM)-induced mouse model of the disease. Through improved and novel studies of animal disease models, more effective diagnostic and treatment strategies may be developed for clinical translation. We introduce use of a miniaturized multimodal endoscope with lavage-delivered fluorescent probes to examine dynamic microenvironment changes in an AOM-treated mouse model.
  
  
  METHODS
  The endoscope is equipped with optical coherence tomography (OCT) and laser induced fluorescence (LIF) imaging modalities. It is used with Cy5.5-conjugated antibodies to create time-resolved molecular maps of colon carcinogenesis. We monitored in vivo changes in molecular expression over a five month period for four biomarkers: epithelial growth factor receptor (EGFR), transferrin receptor (TfR), transforming growth factor beta 1 (TGFβ1), and chemokine (C-X-C motif) receptor 2 (CXCR2). In vivo OCT and LIF images were compared over multiple time points to correlate increases in biomarker expression with adenoma development.
  
  
  RESULTS
  This system is uniquely capable of tracking in vivo changes in molecular expression over time. Increased expression of the biomarker panel corresponded to sites of disease and offered predictive utility in highlighting sites of disease prior to detectable structural changes. Biomarker expression also tended to increase with higher tumor burden and growth rate in the colon.
  
  
  CONCLUSIONS
  We can use miniaturized dual modality endoscopes with fluorescent probes to study the tumor microenvironment in developmental animal models of cancer and supplement findings from biopsy and tissue harvesting.
authors.affiliation: Department of Biomedical Engineering, University of Arizona, Tucson, AZ.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Leung
authors.forename: Photini S
authors.initials: PS
authors.lastname: Rice
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Barton
mesh_terms: D000818:Animals; D001397:Azoxymethane; D014408:Biomarkers, Tumor / Q000378:metabolism*; D063646:Carcinogenesis / Q000139:chemically induced / Q000378:metabolism*; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D020685:Colonoscopes; D003113:Colonoscopy / Q000295:instrumentation / Q000379:methods*; D018450:Disease Progression; D005260:Female; D051379:Mice; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000295:instrumentation / Q000379:methods*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D001397:Azoxymethane
keywords: endoscopy; fluorescence; microenvironment; molecular imaging; optical coherence tomography