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First published online September 15, 2008, 10.2967/jnumed.107.049536
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Journal of Nuclear Medicine Vol. 49 No. 10 1677-1685
© 2008 by Society of Nuclear Medicine
doi: 10.2967/jnumed.107.049536

Basic Science Investigation

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

Seigo Ishino1, Takahiro Mukai2, Yuji Kuge1, Noriaki Kume3, Mikako Ogawa4, Nozomi Takai1, Junko Kamihashi1, Masashi Shiomi5, Manabu Minami3, Toru Kita3 and Hideo Saji1

1 Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; 2 Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; 3 Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 4 Laboratory of Genome Bio-Photonics Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan; and 5 Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Japan

Correspondence: For correspondence or reprints contact: Hideo Saji, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. E-mail: hsaji{at}pharm.kyoto-u.ac.jp

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 99mTc-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 99mTc after derivatization with 6-hydrazinonicotinic acid to yield 99mTc-LOX-1-mAb and 99mTc-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 99mTc-LOX-1-mAb accumulation was 2.0-fold higher than the level of 99mTc-IgG2a accumulation in WHHLMI rabbit aortas, and the level of 99mTc-LOX-1-mAb accumulation in WHHLMI rabbit aortas was 10.0-fold higher than the level of 99mTc-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 99mTc-IgG2a accumulation was independent of the histologic grade of the lesions; however, regional 99mTc-LOX-1-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/mm2)/[injected radioactivity (Bq)/animal body weight (g)]} x 102, 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 99mTc-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 99mTc-LOX-1-mAb may be a useful means for predicting atheroma at high risk for rupture.

Key Words: plaque • receptor • antibody • imaging • atherosclerosis

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.


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