title: Detection of intestinal cancer by local, topical application of a quenched fluorescence probe for cysteine cathepsins.
abstract: Early detection of colonic polyps can prevent up to 90% of colorectal cancer deaths. Conventional colonoscopy readily detects the majority of premalignant lesions, which exhibit raised morphology. However, lesions that are flat and depressed are often undetected using this method. Therefore, there is a need for molecular-based contrast agents to improve detection rates over conventional colonoscopy. We evaluated a quenched fluorescent activity-based probe (qABP; BMV109) that targets multiple cysteine cathepsins that are overexpressed in intestinal dysplasia in a genetic model of spontaneous intestinal polyp formation and in a chemically induced model of colorectal carcinoma. We found that the qABP selectively targets cysteine cathepsins, resulting in high sensitivity and specificity for intestinal tumors in mice and humans. Additionally, the qABP can be administered by either intravenous injection or by local delivery to the colon, making it a highly valuable tool for improved detection of colorectal lesions using fluorescence-guided colonoscopy.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Ehud
authors.initials: E
authors.lastname: Segal
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Tyler R
authors.initials: TR
authors.lastname: Prestwood
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Wouter A
authors.initials: WA
authors.lastname: van der Linden
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Carmi
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Nupur
authors.initials: N
authors.lastname: Bhattacharya
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Nimali
authors.initials: N
authors.lastname: Withana
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Martijn
authors.initials: M
authors.lastname: Verdoes
authors.affiliation: Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Aida
authors.initials: A
authors.lastname: Habtezion
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
authors.affiliation: Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. Electronic address: mbogyo@stanford.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bogyo
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D020134:Catalytic Domain; D002403:Cathepsins / Q000737:chemistry* / Q000378:metabolism; D003113:Colonoscopy; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011127:Polyps / Q000737:chemistry / Q000175:diagnosis / Q000473:pathology; D012680:Sensitivity and Specificity
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D002232:Carbocyanines; D005456:Fluorescent Dyes; C085321:cyanine dye 5; D002403:Cathepsins