Chemotactic cytokines, such as monocyte chemoattractant protein-1 (chemotactic protein-1; MCP-1), play a pivotal role in the inflammatory process associated with the development and progression of atherosclerosis (1, 2). MCP-1, a low molecular weight monomeric peptide (9–15 kDa), is initially upregulated at the site of vessel wall injury by vascular smooth muscle cells (SMC) and endothelial cells (3). MCP-1, in interaction with several cytokines and cell adhesion molecules, mediates the transendothelial migration of monocytes to the subendothelial layer via cysteine-cysteine motif chemokine receptor-2 (CCR-2) receptor (4-7). As a response to the chemotactic signal, monocytes upregulate the number of CCR-2 receptors on their cell surface (8). The recruited monocytes then express MCP-1 by themselves, which accelerates the further influx of mononuclear cells. Once resident within the neointima, the monocytes differentiate to macrophages, express matrix metalloproteinases (MMPs), transform to foam cells by digesting oxidized low-density lipoproteins via expression of scavenger receptors, and form a necrotic core by undergoing apoptosis or necrosis (1). The MMPs expressed by macrophages and foam cells induce dissolution of SMCs and collagen, which causes the plaque cap to thin and makes the cap susceptible to rupture (9, 10). Because the extent of macrophage inflammation in atherosclerotic plaque is positively related to plaque instability, and because the receptor for MCP-1 is only expressed by infiltrating monocytes, the detection of MCP-1 receptors should allow monitoring of the extent of inflammation in atherosclerotic plaque. The use of radiolabeled MCP-1 for non-invasive imaging of the CCR-2 receptor density in atherosclerotic plaque might provide to be a useful clinical tool for the detection of plaques vulnerable to rupture.
Ohtsuki et al. (11) demonstrated the feasibility of using 125I-MCP-1 to identify lesional monocytes and macrophages in experimental atherosclerosis with autoradiography. Blankenberg et al. (12) successfully labeled recombinant human MCP-1 with 99mTc using the nicotinic acid analog hydrazinonicotinamide (HYNIC) as the chelator. The study demonstrated that 99mTc-MCP-1 could detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. Kown et al. (13) reported that 99mTc-MCP-1 could be used to assess graft coronary artery disease in rats. Hartung et al. (14) evaluated 99mTc-MCP-1 for detection of inflammation in rabbits with induced atherosclerotic lesions. The study concluded that non-invasive detection of inflammation in experimental atherosclerotic lesions was feasible using 99mTc-MCP-1.