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Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

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Abstract

Purpose

Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of 99mTc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits).

Methods

Anti-MT1-MMP monoclonal IgG3 and negative control IgG3 were radiolabelled with 99mTc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield 99mTc-MT1-MMP mAb and 99mTc-IgG3, respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed.

Results

99mTc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional 99mTc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while 99mTc-IgG3 accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest 99mTc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID×BW/mm2 × 102), followed in decreasing order by fibroatheromatous (1.8 ± 1.3), collagen-rich (1.6 ± 1.0) and neointimal lesions (1.5 ± 1.5). In contrast, 99mTc-IgG3 accumulation was almost independent of the histological grade of lesions.

Conclusion

Higher 99mTc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with 99mTc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required.

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Acknowledgments

This work was partly supported by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and from the Japan Society for the Promotion of Science, and by a research grant from New Energy and Industrial Technology Development Organization (NEDO). This study was also partly supported by Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government.

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Authors and Affiliations

  1. Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

    Yuji Kuge, Nozomi Takai, Yuki Ogawa, Takashi Temma, Kantaro Nishigori, Seigo Ishino, Junko Kamihashi, Yasushi Kiyono & Hideo Saji

  2. Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Yuji Kuge & Yan Zhao

  3. Central Institute of Isotope Science, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-0815, Japan

    Yuji Kuge

  4. Biomedical Imaging Research Center, University of Fukui, Fukui, Japan

    Yasushi Kiyono

  5. Institute for Experimental Animals, Kobe University Graduate School of Medicine, Kobe, Japan

    Masashi Shiomi

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  1. Yuji Kuge
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  2. Nozomi Takai
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  3. Yuki Ogawa
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Correspondence to Yuji Kuge.

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Kuge, Y., Takai, N., Ogawa, Y. et al. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques. Eur J Nucl Med Mol Imaging 37, 2093–2104 (2010). https://doi.org/10.1007/s00259-010-1521-2

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