title: In vivo Overhauser-enhanced MRI of proteolytic activity.
abstract: There is an increasing interest in developing novel imaging strategies for sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled macromolecules thanks to a sharp decrease of the rotational correlation time of the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in vivo at 0.2 T using nitroxide-labeled elastin orally administered in mice. In vitro, this elastin derivative was OMRI-visible and gave rise to high Overhauser enhancements (19-fold at 18 mm nitroxide) upon proteolysis by pancreatic porcine elastase. In vivo three-dimensional OMRI detection of proteolysis was carried out. A keyhole fully balanced steady-state free precession sequence was used, which allowed 3D OMRI acquisition within 20 s at 0.125 mm(3) resolution. About 30 min after mouse gavage, proteolysis was detected in the duodenum, where Overhauser enhancements were 7.2 ± 2.4 (n = 7) and was not observed in the stomach. Conversely, orally administered free nitroxides or pre-digested nitroxide-labeled elastin were detected in the mouse's stomach by OMRI. Combined with specific molecular probes, this Overhauser-enhanced MRI technique can be used to evaluate unregulated proteolytic activities in various models of experimental diseases and for drug testing.
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Neha
authors.initials: N
authors.lastname: Koonjoo
authors.forename: Elodie
authors.initials: E
authors.lastname: Parzy
authors.forename: Philippe
authors.initials: P
authors.lastname: Massot
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lepetit-Coiffé
authors.forename: Sylvain R A
authors.initials: SR
authors.lastname: Marque
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Franconi
authors.forename: Eric
authors.initials: E
authors.lastname: Thiaudiere
authors.forename: Philippe
authors.initials: P
authors.lastname: Mellet
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D004549:Elastin / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009589:Nitrogen Oxides / Q000737:chemistry*; D059748:Proteolysis; D013113:Spin Labels
chemical_list: D003287:Contrast Media; D009589:Nitrogen Oxides; D013113:Spin Labels; D004549:Elastin; C039900:nitroxyl
keywords: OMRI; in vivo; mouse; proteolytic activity