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

  • Yuji Kuge
  • Nozomi Takai
  • Yuki Ogawa
  • Takashi Temma
  • Yan Zhao
  • Kantaro Nishigori
  • Seigo Ishino
  • Junko Kamihashi
  • Yasushi Kiyono
  • Masashi Shiomi
  • Hideo Saji
Original Article

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

Atherosclerosis Imaging Matrix metalloproteinase Antibody Rabbit 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Yuji Kuge
    • 1
    • 2
    • 3
  • Nozomi Takai
    • 1
  • Yuki Ogawa
    • 1
  • Takashi Temma
    • 1
  • Yan Zhao
    • 2
  • Kantaro Nishigori
    • 1
  • Seigo Ishino
    • 1
  • Junko Kamihashi
    • 1
  • Yasushi Kiyono
    • 1
    • 4
  • Masashi Shiomi
    • 5
  • Hideo Saji
    • 1
  1. 1.Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  2. 2.Department of Tracer Kinetics & Bioanalysis, Graduate School of MedicineHokkaido UniversitySapporoJapan
  3. 3.Central Institute of Isotope ScienceHokkaido UniversitySapporoJapan
  4. 4.Biomedical Imaging Research CenterUniversity of FukuiFukuiJapan
  5. 5.Institute for Experimental AnimalsKobe University Graduate School of MedicineKobeJapan

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