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Overhauser-enhanced MRI of elastase activity from in vitro human neutrophil degranulation.

PloS one (2013-03-08)
Elodie Parzy, Véronique Bouchaud, Philippe Massot, Pierre Voisin, Neha Koonjoo, Damien Moncelet, Jean-Michel Franconi, Eric Thiaudière, Philippe Mellet
ABSTRACT

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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Elastin from bovine neck ligament, powder
Sigma-Aldrich
Elastin, soluble from bovine neck ligament, salt-free, lyophilized powder
Sigma-Aldrich
Elastin from human skin, insoluble powder
Sigma-Aldrich
Elastin, soluble from human lung, lyophilized powder
Sigma-Aldrich
Elastin, soluble from human aorta, lyophilized powder
Sigma-Aldrich
Elastin from mouse lung, powder