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

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European Journal of Nuclear Medicine and Molecular Imaging

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01-11-2010 | Original Article

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

Authors: Yuji Kuge, Nozomi Takai, Yuki Ogawa, Takashi Temma, Yan Zhao, Kantaro Nishigori, Seigo Ishino, Junko Kamihashi, Yasushi Kiyono, Masashi Shiomi, Hideo Saji

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2010

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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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Title: Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques
Authors: Yuji Kuge
Nozomi Takai
Yuki Ogawa
Takashi Temma
Yan Zhao
Kantaro Nishigori
Seigo Ishino
Junko Kamihashi
Yasushi Kiyono
Masashi Shiomi
Hideo Saji
Publication date: 01-11-2010
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2010
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-010-1521-2

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