| Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques. | |
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MedLine Citation:
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PMID: 20625725 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (99m)Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). METHODS: Anti-MT1-MMP monoclonal IgG(3) and negative control IgG(3) were radiolabelled with (99m)Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield (99m)Tc-MT1-MMP mAb and (99m)Tc-IgG(3), 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: (99m)Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional (99m)Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while (99m)Tc-IgG(3) accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest (99m)Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID×BW/mm(2) × 10(2)), 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, (99m)Tc-IgG(3) accumulation was almost independent of the histological grade of lesions. CONCLUSION: Higher (99m)Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with (99m)Tc-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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Authors:
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Yuji Kuge; Nozomi Takai; Yuki Ogawa; Takashi Temma; Yan Zhao; Kantaro Nishigori; Seigo Ishino; Junko Kamihashi; Yasushi Kiyono; Masashi Shiomi; Hideo Saji |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-13 |
Journal Detail:
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Title: European journal of nuclear medicine and molecular imaging Volume: 37 ISSN: 1619-7089 ISO Abbreviation: Eur. J. Nucl. Med. Mol. Imaging Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2011-01-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101140988 Medline TA: Eur J Nucl Med Mol Imaging Country: Germany |
Other Details:
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Languages: eng Pagination: 2093-104 Citation Subset: IM |
Affiliation:
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Department of Patho-functional Bioanalysis, Kyoto University, Kyoto, Japan. kuge@ric.hokudai.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / chemistry, diagnostic use, immunology* Humans Immunoglobulin G / chemistry, diagnostic use, immunology Male Matrix Metalloproteinase 14 / immunology* Molecular Imaging / methods* Niacin / chemistry Organotechnetium Compounds / diagnostic use Plaque, Atherosclerotic / diagnosis, metabolism*, pathology Rabbits |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Immunoglobulin G; 0/Organotechnetium Compounds; 59-67-6/Niacin; EC 3.4.24.80/Matrix Metalloproteinase 14 |
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