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First published online October 17, 2007, 10.2967/jnumed.107.043463
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Journal of Nuclear Medicine Vol. 48 No. 11 1816-1821
© 2007 by Society of Nuclear Medicine

doi: 10.2967/jnumed.107.043463

Basic Science Investigation

Radiolabeled Monocyte Chemotactic Protein 1 for the Detection of Inflammation in Experimental Atherosclerosis

Dagmar Hartung1, Artiom Petrov1, Nezam Haider1, Shinichiro Fujimoto1, Francis Blankenberg2, Ai Fujimoto1, Renu Virmani3, Frank D. Kolodgie3, H. William Strauss4 and Jagat Narula1

1 University of California School of Medicine, Irvine, California; 2 Stanford University Medical Center, Stanford, California; 3 International Registry of Pathology, Gaithersburg, Maryland; and 4 Memorial Sloan-Kettering Cancer Center, New York, New York

Correspondence: For correspondence or reprints contact: Artiom Petrov, PhD, University of California, Irvine, School of Medicine, C116 Medical Science I, Irvine, CA 92697. E-mail: adpetrov{at}uci.edu

Chemotactic peptides, such as Monocyte Chemotactic Protein 1 (MCP-1), play a key role in transendothelial migration of mononuclear cells during the development and progression of atherosclerotic disease. Because atherosclerotic plaques that are precursors of acute coronary events harbor abundant macrophage infiltration, we hypothesized that the detection of a high concentration of MCP-1 receptors on inflammatory cells should noninvasively identify vulnerable plaques. Methods: Atherosclerotic lesions were induced by balloon deendothelialization of the abdominal aorta, which was followed by a 0.5% cholesterol diet for 16 wk in 7 New Zealand White rabbits; 5 unmanipulated rabbits, fed normal chow for 16 wk, were used as controls. Radionuclide imaging was performed immediately after intravenous 99mTc-labeled MCP-1 administration and 3 h later. At the end of imaging session, aortas were explanted and submitted for estimation of quantitative MCP-1 uptake (in percentage injected dose per gram, %ID/g) and pathologic characterization. Results: Atherosclerotic lesions were clearly visible in all hyperlipidemic animal {gamma}-imaging. No tracer uptake was seen in the control rabbits. The mean quantitative MCP-1 uptake in atherosclerotic lesions was 4-fold higher than that of the aortic specimens from the control rabbits (0.065 ± 0.005 vs. 0.016 ± 0.006; P < 0.0001). Histology confirmed a strong correlation between MCP-1 uptake and the number of macrophages in American Heart Association type II–IV lesions (r = 0.87, P < 0.0001). Conclusion: Noninvasive radionuclide imaging of inflammation is feasible by MCP-1 in experimentally induced atherosclerosis. It is proposed that detection of the extent of inflammation in advanced atherosclerotic plaques may allow identification of unstable plaques.

Key Words: inflammation • vulnerable plaque • cytokines • coronary artery disease

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.


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