Novel MRI and fluorescent probes responsive to the Factor XIII transglutaminase activity.
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.
Tei
Lorenzo
L
Dipartimento di Scienze dell'Ambiente e della Vita, Università del Piemonte Orientale, Viale T. Michel 11, I-15121, Alessandria, Italy.
Mazooz
Galit
G
Shellef
Yael
Y
Avni
Reut
R
Vandoorne
Katrien
K
Barge
Alessandro
A
Kalchenko
Vyacheslav
V
Dewhirst
Mark W
MW
Chaabane
Linda
L
Miragoli
Luigi
L
Longo
Dario
D
Neeman
Michal
M
Aime
Silvio
S
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*
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