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Human myeloperoxidase: A potential target for molecular MR imaging in atherosclerosis
Author(s) -
Chen John W.,
Pham Wellington,
Weissleder Ralph,
Bogdanov Alexei
Publication year - 2004
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.20270
Subject(s) - myeloperoxidase , chemistry , conjugate , polymerization , covalent bond , biochemistry , pathology , inflammation , medicine , immunology , mathematical analysis , mathematics , organic chemistry , polymer
Plaque rupture in atherosclerotic disease is the major cause of morbidity and correlates well with myeloperoxidase (MPO) secretion by activated neutrophils and macrophages in humans. We hypothesized that paramagnetic electron donor compounds that rapidly oxidize and polymerize in the presence of MPO could be designed to enable imaging of local MPO activity levels in arterial segments at risk. Several potential substrates for MPO were synthesized and tested. One lead compound consisting of a covalent conjugate of GdDOTA and serotonin (3‐(2‐aminoethyl)‐5‐hydroxyindole) was efficiently polymerized in the presence of human neutrophil MPO resulting in a 70–100% increase in proton relaxivity. As a result, we were able to demonstrate MPO activity in enzyme solutions and in a model tissue‐like system. These studies suggest that activatable paramagnetic MR imaging agents can be used to directly image MPO activity. Magn Reson Med 52:1021–1028, 2004. © 2004 Wiley‐Liss, Inc.