title: Early detection of colonic dysplasia by magnetic resonance molecular imaging with a contrast agent raised against the colon cancer marker MUC5AC.
abstract: Human gastric mucin MUC5AC is secreted in the colonic mucus of cancer patients and is a specific marker of precancerous lesions called aberrant crypt foci. Using MUC5AC as a specific marker can improve sensitivity in the detection of early colorectal cancer. Here we demonstrated that the accumulation of MUC5AC in xenograft and mouse stomach can be detected by magnetic resonance imaging (MRI). We used ultrasmall particles of iron oxide (USPIOs) conjugated with disulfide constrained heptapeptide that were identified using a screening phage display. To accomplish this, we employed positive selection of the phage display library on MUC5AC purified from fresh human colonic adenomas in combination with negative selection of the phage library on purified human MUC2, which is predominantly found in normal colorectal tissues. This conjugate was tested on human colorectal cancer cell lines that were either able or unable to secrete MUC5AC, both in vitro and in vivo. MUC5AC-USPIO contrast agent and USPIOs alone were not detected in cell lines unable to secrete MUC5AC. A combination of MRI and microscopy studies was performed to detect a specific accumulation of the contrast agent in vivo. Thus, the MUC5AC contrast agent enabled non-invasive detection of precancerous lesions and colorectal cancer, highlighting its potential use in diagnostics, in the early detection of colorectal cancer recurrences after treatment and in mechanistic studies implicating MUC5AC. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: University of Lille Nord de France, F-59000, Lille, France.|USTL, UGSF, IFR 147, F-59650, Villeneuve d'Ascq, France.|CNRS, UMR 8576, F-59650, Villeneuve d'Ascq, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Rossez
authors.affiliation: Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 19, Avenue Maistriau, Mendeleev Building, B-7000, Mons, Belgium.
authors.forename: Carmen
authors.initials: C
authors.lastname: Burtea
authors.affiliation: Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 19, Avenue Maistriau, Mendeleev Building, B-7000, Mons, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
authors.affiliation: University of Lille Nord de France, F-59000, Lille, France.|UCLille, Service d'Anatomie Pathologie, F-59000, Lille, France.|Groupe Hospitalier de l'Institut Catholique Lillois/Faculté Libre de Médecine, F-59000, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gosset
authors.affiliation: University of Lille Nord de France, F-59000, Lille, France.|USTL, UGSF, IFR 147, F-59650, Villeneuve d'Ascq, France.|CNRS, UMR 8576, F-59650, Villeneuve d'Ascq, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Léonard
authors.affiliation: Guerbet, Research Center, 16-24 rue Jean Chaptal, 93600, Aulnay-sous-Bois, France.
authors.forename: Walter
authors.initials: W
authors.lastname: Gonzalez
authors.affiliation: Guerbet, Research Center, 16-24 rue Jean Chaptal, 93600, Aulnay-sous-Bois, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ballet
authors.affiliation: Guerbet, Research Center, 16-24 rue Jean Chaptal, 93600, Aulnay-sous-Bois, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raynal
authors.affiliation: Guerbet, Research Center, 16-24 rue Jean Chaptal, 93600, Aulnay-sous-Bois, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rousseaux
authors.affiliation: Groupe Hospitalier de l'Institut Catholique Lillois/Faculté Libre de Médecine, F-59000, Lille, France.
authors.forename: Timothée
authors.initials: T
authors.lastname: Dugué
authors.affiliation: Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 19, Avenue Maistriau, Mendeleev Building, B-7000, Mons, Belgium.
authors.forename: Luce
authors.initials: L
authors.lastname: Vander Elst
authors.affiliation: University of Lille Nord de France, F-59000, Lille, France.|USTL, UGSF, IFR 147, F-59650, Villeneuve d'Ascq, France.|CNRS, UMR 8576, F-59650, Villeneuve d'Ascq, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.affiliation: Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 19, Avenue Maistriau, Mendeleev Building, B-7000, Mons, Belgium.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Muller
authors.affiliation: University of Lille Nord de France, F-59000, Lille, France.|USTL, UGSF, IFR 147, F-59650, Villeneuve d'Ascq, France.|CNRS, UMR 8576, F-59650, Villeneuve d'Ascq, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Robbe-Masselot
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging; D003287:Contrast Media / Q000737:chemistry*; D055088:Early Detection of Cancer / Q000379:methods; D064593:Heterografts; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D055271:Mucin 5AC / Q000032:analysis*; D055262:Mucin-2; D019151:Peptide Library; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D019151:Peptide Library
keywords: MRI; MUC5AC; biomarkers; colorectal cancer; mucin