Detection of monocyte chemoattractant protein-1 receptor expression in experimental atherosclerotic lesions - An autoradiographic study

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 I-125-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). I-125-MCP-1 has a blood clearance half-time of approximate to 10 minutes and circulates in association with cells. The liver, lungs, and kidneys had the highest concentration of I-125-MCP-1 at 5 and 30 minutes after tracer administration, Autoradiograms revealed accumulation of I-125-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 I-125-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 I-125-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.