title: Novel MRI and fluorescent probes responsive to the Factor XIII transglutaminase activity.
abstract: Transglutaminases, including factor XIII and tissue transglutaminase, participate in multiple extracellular processes associated with remodeling of the extracellular matrix during wound repair, blood clotting, tumor progression and fibrosis of ischemic injuries. The aim of this work was to evaluate a novel substrate analog for transglutaminase optimized by molecular modeling calculations (DCCP16), which can serve for molecular imaging of transglutaminase activity by magnetic resonance imaging and by near-infrared imaging. Experimental data showed covalent binding of Gd-DCCP16 and DCCP16-IRIS Blue to human clots, to basement membrane components and to casein in purified systems as well as in three-dimensional multicellular spheroids. In vivo, DCCP16 showed enhancement with a prolonged retention in clots and tumors, demonstrating the ability to detect both factor XIII and tissue transglutaminase mediated covalent binding of the contrast material.
authors.affiliation: Dipartimento di Scienze dell'Ambiente e della Vita, Università del Piemonte Orientale, Viale T. Michel 11, I-15121, Alessandria, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Tei
authors.forename: Galit
authors.initials: G
authors.lastname: Mazooz
authors.forename: Yael
authors.initials: Y
authors.lastname: Shellef
authors.forename: Reut
authors.initials: R
authors.lastname: Avni
authors.forename: Katrien
authors.initials: K
authors.lastname: Vandoorne
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barge
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Kalchenko
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: Linda
authors.initials: L
authors.lastname: Chaabane
authors.forename: Luigi
authors.initials: L
authors.lastname: Miragoli
authors.forename: Dario
authors.initials: D
authors.lastname: Longo
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D005176:Factor XIII / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000378:metabolism; D011503:Transglutaminases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; C556413:DCCP16-Iris Blue; D005456:Fluorescent Dyes; D007211:Indoles; D010455:Peptides; C556412:gadolinium DCCP16 compound; D005176:Factor XIII; D011503:Transglutaminases