Radioimmunodetection of Membrane Type-1 Matrix Metalloproteinase Relevant to Tumor Malignancy with a Pre-targeting Method
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- Sano Kohei
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Temma Takashi
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Kuge Yuji
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University Central Institute of Isotope Science, Hokkaido University
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- Kudo Takashi
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Kamihashi Junko
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
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- Zhao Songji
- Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University
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- Saji Hideo
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
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抄録
Since membrane type-1 matrix metalloproteinase (MT1-MMP) is exclusively expressed in tumors and is closely associated with metastasis and invasion, MT1-MMP is a potential target of radiotracers for the evaluation of tumor malignancy. In this study, we planned to visualize MT1-MMP in vivo by a two-step pre-targeting strategy using a streptavidin (SAv)-biotin system combined with anti-MT1-MMP monoclonal immunoglobulin (IgG) (anti-MT1-MMP monoclonal antibody (mAb)). Streptavidinylated anti-MT1-MMP mAb was synthesized by reacting biotinylated anti-MT1-MMP mAb with SAv. In the pre-targeting study, FM3A mouse breast carcinoma-implanted mice were injected with anti-MT1-MMP mAb-SAv, followed 72 h later with radioiodinated biotin, (3-[123/125I]iodobenzoyl)norbiotinamide (123/125I-IBB). Biodistribution and imaging (single photon emission computed tomography (SPECT)/CT) data were collected at several time points in the 24 h period following introduction of the tracer. The comparison groups were injected with 125I-IBB alone or with 125I-IBB pre-targeted with negative control IgG-SAv. In the pre-targeting study for MT1-MMP, within 1 h of tracer injection, rapid tumor uptake and abrupt clearance from the blood of radioactivity (2.22, 0.87% injected dose/g at 1 h) were observed. The tumor to blood (T/B) radioactivity ratios were significantly higher than those from mice dosed with the pre-targeting negative control (p<0.0001). 125I-IBB alone did not accumulate in tumors. SPECT/CT image analysis of FM3A bearing mice showed high-contrast tumor images after 3 h with minimal blood-pool activity. The present study that uses a pre-targeting method showed high T/B radioactivity ratios and clear tumor images of MT1-MMP. This imaging method may be useful for the clinical diagnosis of malignant tumors.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 33 (9), 1589-1595, 2010
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679603399168
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- NII論文ID
- 130000322361
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 10796999
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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