Targeting of Lectinlike Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) with 99mTc-Labeled Anti–LOX-1 Antibody: Potential Agent for Imaging of Vulnerable Plaque

Lectinlike oxidized low-density lipoprotein (LDL) receptor 1 (LOX-1), a cell surface receptor for oxidized LDL, has been implicated in vascular cell dysfunction related to plaque instability, which could be a potential target for an atherosclerosis imaging tracer. In this study, wedesigned and prepared 99m Tc-labeled anti-LOX-1 monoclonal IgG and investigated its usefulness as an atherosclerosis imaging agent. Methods: Anti-LOX-1 monoclonal IgG and control mouse lgG2a were labeled with 99m Tc after derivatization with 6-hydrazinonicotinic acid to yield 99m Tc-LOX-1-mAb and 99m Tc-lgG2a, respectively. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits (atherosclerosis model) and control rabbits were injected intravenously with these probes, and in vivo planar imaging was performed. At 24 h after the injection, the aortas were removed, and radioactivity was measured. Autoradiography and histologic studies were performed with serial aortic sections. Results: The level of 99m Tc-LOX-1-mAb accumulation was 2.0-fold higher than the level of 9 9m Tc-lgG2a accumulation in WHHLMI rabbit aortas, and the level of 99m Tc-LOX-1-mAb accumulation in WHHLMI rabbit aortas was 10.0-fold higher than the level of 99m Tc-LOX-1-mAb accumulation in control rabbit aortas. In vivo imaging clearly visualized the atherosclerotic aortas of WHHLMI rabbits. Autoradiography and histologic studies revealed that regional 9 9m Tc-lgG2a accumulation was independent of the histologic grade of the lesions; however, regional 99m Tc-LOX-1-mAb accumulation was significantly correlated with LOX-1 expression density and the vulnerability index. The highest level of 99m Tc-LOX-1-mAb accumulation, expressed as {radioactivity in region of interest (Bq/mm 2 )/[injected radioactivity (Bq)/animal body weight (g)]} x 10 2 , was found in atheromatous lesions (3.8 ±1.1 [mean ± SD]), followed in decreasing order by fibroatheromatous lesions (2.0 ± 1.0), collagen-rich lesions (1.6 ± 0.8), and neointimal lesions (1.4 ± 0.7). Conclusion: The level of 99m Tc-LOX-1 -mAb accumulation in grade IV atheroma was higher than that in neointimal lesions or other, more stable lesions. Nuclear imaging of LOX-1 expression with 99m Tc-LOX-I-mAb may be a useful means for predicting atheroma at high risk for rupture.