Development of magnetic resonance imaging contrast material for in vivo mapping of tissue transglutaminase activity.
Transglutaminases are a family of enzymes that play an important role in tissue remodeling by catalyzing covalent cross-links between proteins of the extracellular matrix. Elevated activity of transglutaminase was shown at the boundaries of invading tumors, in association with angiogenesis, in stabilization of atherosclerotic plaques, and in generation of blood clots. The aim of this work was to develop a low molecular weight substrate of transglutaminase that could serve for noninvasive magnetic resonance and optical mapping of transglutaminase-mediated cross-linking activity. A 2 kDa contrast material was generated which showed cross-linking by either tissue transglutaminase or factor XIII in the context of multicellular tumor spheroids or fibrin clots, respectively. Successful detection by nuclear magnetic resonance microscopy of transglutaminase-mediated cross-linking of the contrast material to MCF7 multicellular spheroids provides hope that this approach could potentially be developed for clinical demarcation of sites of transglutaminase activity.
Mazooz
Galit
G
Department of Biological Regulation and Biological Services, The Weizmann Institute of Science, Rehovot 76100, Israel.
Mehlman
Tevie
T
Lai
Thung-Shen
TS
Greenberg
Charles S
CS
Dewhirst
Mark W
MW
Neeman
Michal
M
D001943:Breast Neoplasms / Q000201:enzymology; D045744:Cell Line, Tumor; D003287:Contrast Media; D019786:Gadolinium DTPA / Q000031:analogs & derivatives; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008970:Molecular Weight; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D018874:Spheroids, Cellular / Q000201:enzymology; D013379:Substrate Specificity; D011503:Transglutaminases / Q000378:metabolism*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D003287:Contrast Media; D009842:Oligopeptides; D010446:Peptide Fragments; D000979:alpha-2-Antiplasmin; D011503:Transglutaminases; D019786:Gadolinium DTPA; D008239:Lysine