title: New concepts in molecular imaging: non-invasive MRI spotting of proteolysis using an Overhauser effect switch.
abstract: BACKGROUND
  Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies.
  
  
  RESULTS
  In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI) at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans.
  
  
  CONCLUSIONS
  The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases.
authors.affiliation: INSERM IFR 004, and Magnetic Resonance Center CNRS UMR 5536 University Victor Segalen Bordeaux, Bordeaux, France. philippe.mellet@rmsb.u-bordeaux2.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Mellet
authors.forename: Philippe
authors.initials: P
authors.lastname: Massot
authors.forename: Guillaume
authors.initials: G
authors.lastname: Madelin
authors.forename: Sylvain R A
authors.initials: SR
authors.lastname: Marque
authors.forename: Etienne
authors.initials: E
authors.lastname: Harte
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Franconi
authors.forename: Eric
authors.initials: E
authors.lastname: Thiaudière
mesh_terms: D000818:Animals; D002417:Cattle; D003545:Cysteine / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D006868:Hydrolysis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D055641:Mathematical Concepts; D008954:Models, Biological; D009589:Nitrogen Oxides / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D009589:Nitrogen Oxides; D011506:Proteins; D012710:Serum Albumin, Bovine; D010447:Peptide Hydrolases; C039900:nitroxyl; D003545:Cysteine