Development of Magnetic Resonance Imaging Contrast Material forIn vivoMapping of Tissue Transglutaminase Activity

Galit Mazooz, Tevie Mehlman, Thung-Shen Lai, Charles S. Greenberg, Mark W. Dewhirst, Michal Neeman
2005 Cancer Research  
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
more » ... c resonance and optical mapping of transglutaminase-mediated cross-linking activity. A 2 kDa contrast material was generated which showed crosslinking 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. (Cancer Res 2005; 65(4): 1369-75)
doi:10.1158/0008-5472.can-04-2269 pmid:15735023 fatcat:e62om222lja2bcj73jqoyeghaa