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(Circulation. 2008;117:388-395.)
© 2008 American Heart Association, Inc.

Imaging

Noninvasive In Vivo Imaging of Monocyte Trafficking to Atherosclerotic Lesions

Moritz F. Kircher, MD; Jan Grimm, MD, PhD; Filip K. Swirski, PhD; Peter Libby, MD; Robert E. Gerszten, MD; Jennifer R. Allport, PhD; Ralph Weissleder, MD, PhD

From the Center for Molecular Imaging Research (M.F.K., J.G., F.K.S., R.E.G., J.R.A., R.W.), Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass; Center for Systems Biology (R.W.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass; Cardiovascular Division (F.K.S., P.L.), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; Cardiovascular Research Center (R.E.G.), Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass; and Donald W. Reynolds Cardiovascular Clinical Research Center on Atherosclerosis at Harvard Medical School (F.K.S., P.L., R.E.G., R.W.), Boston, Mass. Dr Kircher is currently with the Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass; Dr Grimm is currently with the Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; and Dr Allport is currently with the Novartis Institutes for BioMedical Research Inc, Cambridge, Mass.

Correspondence to Ralph Weissleder, MD, PhD, Center for Systems Biology, Massachusetts General Hospital, Richard B. Simches Research Center, 185 Cambridge St, 8th Floor, Boston, MA 02114. E-mail rweissleder{at}mgh.harvard.edu

Received June 11, 2007; accepted October 30, 2007.

Background— Monocytes play a key role in atherogenesis, but their participation has been discerned largely via ex vivo analyses of atherosclerotic lesions. We sought to establish a noninvasive technique to determine monocyte trafficking to atherosclerotic lesions in live animals.

Methods and Results— Using a micro–single-photon emission computed tomography small-animal imaging system and a Food and Drug Administration–approved radiotracer ([indium 111] oxyquinoline, ¹¹¹In-oxine), we demonstrate here that monocyte recruitment to atherosclerotic lesions can be visualized in a noninvasive, dynamic, and 3-dimensional fashion in live animals. We show in vivo that monocytes are recruited avidly to plaques within days of adoptive transfer. Using micro–single-photon emission computed tomography imaging as a screening tool, we were able to investigate modulatory effects on monocyte recruitment in live animals. We found that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors rapidly and substantially reduce monocyte recruitment to existing atherosclerotic lesions, as imaged here in vivo.

Conclusions— This novel approach to track monocytes to atherosclerotic plaques in vivo should have broad applications and create new insights into the pathogenesis of atherosclerosis and other inflammatory diseases.

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