European Journal of Nuclear Medicine and Molecular Imaging

, Volume 37, Issue 11, pp 2093–2104

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

Authors

    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
    • Department of Tracer Kinetics & Bioanalysis, Graduate School of MedicineHokkaido University
    • Central Institute of Isotope ScienceHokkaido University
  • Nozomi Takai
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
  • Yuki Ogawa
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
  • Takashi Temma
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
  • Yan Zhao
    • Department of Tracer Kinetics & Bioanalysis, Graduate School of MedicineHokkaido University
  • Kantaro Nishigori
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
  • Seigo Ishino
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
  • Junko Kamihashi
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
  • Yasushi Kiyono
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
    • Biomedical Imaging Research CenterUniversity of Fukui
  • Masashi Shiomi
    • Institute for Experimental AnimalsKobe University Graduate School of Medicine
  • Hideo Saji
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto University
Original Article

DOI: 10.1007/s00259-010-1521-2

Cite this article as:
Kuge, Y., Takai, N., Ogawa, Y. et al. Eur J Nucl Med Mol Imaging (2010) 37: 2093. doi:10.1007/s00259-010-1521-2

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.

Keywords

AtherosclerosisImagingMatrix metalloproteinaseAntibodyRabbit

Copyright information

© Springer-Verlag 2010