INOR 302 |
| John W. Chen, Wellington Pham, Ralph Weissleder, and Alexei A. Bogdanov Jr.. Center for Molecular Imaging Research/Radiology, Massachusetts General Hospital, CNY-5420, Charlestown, MA 02129 |
| Plaque rupture in atherosclerotic disease is the major cause of morbidity that correlates well with myeloperoxidase (MPO) secretion by activated neutrophils in humans. We hypothesized that by using paramagnetic electron donor compounds that rapidly oxidize and polymerize in the presence of the enzyme, MPO activity could be imaged using T1-weighted MR imaging. The signal of polymerized paramagnetic MPO substrate is higher than non-polymerized due to the slower rotation of chelated paramagnetic cations. We synthesized an MPO-responsive probe based on 3-(2-aminoethyl)-5-hydroxyindole. The obtained probe (HEIA-DOTA-Gd) was rapidly oxidized in the presence of human MPO with the resultant 1.8-2 fold increase of gadolinium relaxivity and could be imaged at 1.5T. Using a tissue model system we observed MPO-specific increase of MR signal at the interface between the gel and substrate solution consistent with the accumulation of MPO-polymerized HIEA-GdDOTA. Preliminary data suggests that MPO in plaques could be potentially visualized using contrast-enhanced MRI. |
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The Chemistry of Biological Molecular Imaging
8:30 AM-12:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- 108B, Oral
Division of Inorganic Chemistry |