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(Circulation. 2001;104:203.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Detection of Monocyte Chemoattractant Protein-1 Receptor Expression in Experimental Atherosclerotic Lesions

An Autoradiographic Study

Katsuichi Ohtsuki, MD; Motoya Hayase, MD; Koichi Akashi, MD; Susan Kopiwoda, MS; H. William Strauss, MD

From the Division of Nuclear Medicine, Department of Radiology (K.O., S.K., H.W.S.), the Division of Cardiovascular Medicine, Department of Medicine (M.H.), and the Departments of Pathology and Developmental Medicine (K.A.), Stanford University School of Medicine, Stanford, Calif.

Correspondence to H. William Strauss, MD, Division of Nuclear Medicine, Stanford University Medical Center, Room H-0101, 300 Pasteur Dr, Stanford, CA 94305. billstra{at}leland.stanford.edu

Background—— Monocytes, a common component of atheroma, are attracted to the lesion site in response to chemotactic signals, particularly expression of monocyte chemoattractant peptide 1 (MCP-1). This study assessed the feasibility of using radiolabeled MCP-1 to identify monocytes and macrophages that have localized at sites of experimental arterial lesions.

Methods and Results—— The biodistribution of radiolabeled MCP-1 was determined in normal mice, and localization in experimental atheroma was determined in cholesterol-fed rabbits 4 weeks after arterial injury of the iliac artery (9 rabbits) and the abdominal aorta (1 rabbit). Vessels were harvested and autoradiographed after intravenous administration of ¹²⁵I-labeled MCP-1 and Evans blue dye. The arteries were evaluated histologically by hematoxylin and eosin staining and immune staining with a monoclonal antibody specific for rabbit macrophages (RAM-11). ¹²⁵I-MCP-1 has a blood clearance half-time of 10 minutes and circulates in association with cells. The liver, lungs, and kidneys had the highest concentration of ¹²⁵I-MCP-1 at 5 and 30 minutes after tracer administration. Autoradiograms revealed accumulation of ¹²⁵I-MCP-1 in the damaged artery wall, with an average ratio of lesion to normal vessel of 6:1 (maximum 45:1). The accumulation of ¹²⁵I-MCP-1 in the reendothelialized (plaque formation) areas was greater than in the deendothelialized (Evans blue-positive) areas (6.55±2.26 versus 4.34±1.43 counts/pixel, P<0.05). The uptake of ¹²⁵I-MCP-1 correlated with the number of macrophages per unit area (r=0.85, P<0.0001).

Conclusions—— Radiolabeled MCP-1 may be a useful tracer for imaging monocyte/macrophage-rich experimental atherosclerotic lesions.

Key Words: monocyte chemoattractant proteins • atherosclerosis • macrophages • autoradiography

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