Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 49, Issue 10, Pages 1677-1685Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.107.049536
Keywords
plaque; receptor; antibody; imaging; atherosclerosis
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- New Energy and Industrial Technology Development Organization (NEDO)
- Ministry of Health, Labor and Welfare
- 21st Century COE Program Knowledge Information Infrastructure for Genome Science.
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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, we designed and prepared Tc-99m-labeled anti-LOX-1 monoclonal IgG and investigated its usefulness as an atherosclerosis imaging agent. Methods: Anti-LOX-1 monoclonal IgG and control mouse IgG2a were labeled with Tc-99m after derivatization with 6-hydrazinonicotinic acid to yield Tc-99m-LOX-1-mAb and Tc-99m-IgG2a, 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 Tc-99m-LOX-1-mAb accumulation was 2.0-fold higher than the level of Tc-99m-IgG2a accumulation in WHHLMI rabbit aortas, and the level of Tc-99m-LOX-1-mAb accumulation in WHHLMI rabbit aortas was 10.0-fold higher than the level of Tc-99m-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 Tc-99m-IgG2a accumulation was independent of the histologic grade of the lesions; however, regional Tc-99m-LOX1-mAb accumulation was significantly correlated with LOX-1 expression density and the vulnerability index. The highest level of 99mTc-LOX-1-mAb accumulation, expressed as {radioactivity in region of interest (Bq/mm(2))/[injected radioactivity (Bq)/animal body weight (g)]} x 102, was found in atheromatous lesions (3.8 +/- 1.1 [mean +/- SID]), 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 Tc-99m-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 Tc-99m-LOX-1-mAb may be a useful means for predicting atheroma at high risk for rupture.
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