title: Overhauser-enhanced MRI of elastase activity from in vitro human neutrophil degranulation.
abstract: BACKGROUND
  Magnetic resonance imaging can reveal exquisite anatomical details. However several diseases would benefit from an imaging technique able to specifically detect biochemical alterations. In this context protease activity imaging is one of the most promising areas of research.
  
  
  RESULTS
  We designed an elastase substrate by grafting stable nitroxide free radicals on soluble elastin. This substrate generates a high Overhauser magnetic resonance imaging (OMRI) contrast upon digestion by the target proteases through the modulation of its rotational correlation time. The sensitivity is sufficient to generate contrasted images of the degranulation of neutrophils induced by a calcium ionophore from 2×10(4) cells per milliliter, well under the physiological neutrophils concentrations.
  
  
  CONCLUSIONS
  These ex-vivo experiments give evidence that OMRI is suitable for imaging elastase activity from neutrophil degranulation. Provided that a fast protease-substrate is used these results open the door to better diagnoses of a number of important pathologies (cystic fibrosis, inflammation, pancreatitis) by OMRI or Electron Paramagnetic Resonance Imaging in vivo. It also provides a long-expected method to monitor anti-protease treatments efficiency and help pharmaceutical research.
authors.affiliation: CRMSB, UMR 5536, University Bordeaux Segalen, CNRS, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Parzy
authors.forename: Véronique
authors.initials: V
authors.lastname: Bouchaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Massot
authors.forename: Pierre
authors.initials: P
authors.lastname: Voisin
authors.forename: Neha
authors.initials: N
authors.lastname: Koonjoo
authors.forename: Damien
authors.initials: D
authors.lastname: Moncelet
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Franconi
authors.forename: Eric
authors.initials: E
authors.lastname: Thiaudière
authors.forename: Philippe
authors.initials: P
authors.lastname: Mellet
mesh_terms: D015550:Cell Degranulation; D004549:Elastin / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009504:Neutrophils / Q000166:cytology* / Q000201:enzymology*; D009589:Nitrogen Oxides / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism*; D012399:Rotation
chemical_list: D009589:Nitrogen Oxides; D004549:Elastin; D010196:Pancreatic Elastase; C039900:nitroxyl