Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors
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概要
- 論文の詳細を見る
Membrane type-1 matrix metalloproteinase (MT1-MMP) expressed on the tumor cell surface activates pro-MMP-2 and pro-MMP-13 to exacerbate the malignancy, suggesting its suitability as a target molecule for diagnosis by in vivo molecular imaging. Thus, we prepared radiolabeled anti-MT1-MMP monoclonal antibody (mAb) as a novel radiolabeled probe for detecting MT1-MMP in vivo and evaluated its usefulness in breast tumor-bearing rodents. 99mTc-anti-MT1-MMP mAb was prepared using HYNIC as a bifunctional chelating agent and immunoreactivity was evaluated by flow cytometry. MT1-MMP expression in breast carcinoma cells (rat: Walker-256 and MRMT-1, mouse: FM3A) was measured by Western blotting. In vivo biodistribution was examined for 48 h using tumor-implanted rodents followed by estimation of radiation absorbed by a standard quantitation platform Organ Level Internal Dose Assessment (OLINDA). 99mTc-anti-MT1-MMP mAb was obtained with 84% immunoreactivity to MT1-MMP and more than 92% radiochemical purity. MT1-MMP was highly expressed in all malignant cells. Tumor radioactivity increased with time after administration and reached 3 to 5 times higher values at 24 h post-injection than those at 1 h. Other organs, including the stomach, showed decreasing values over time. Tumor to blood ratios increased with time and reached more than 1.3 at 48 h. The effective dose was <5.0 μSv/MBq. The results suggest that 99mTc-anti-MT1-MMP mAb is a promising probe for future diagnosis of breast tumors by in vivo nuclear medical imaging.
- 日本薬学会の論文
著者
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Saji Hideo
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Temma Takashi
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Sano Kohei
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Kuge Yuji
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Kamihashi Junko
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Takai Nozomi
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Ogawa Yuki
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Ogawa Yuki
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Takai Nozomi
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Kuge Yuji
Department Of Tracer Kinetics Hokkaido University School Of Medicine
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Kuge Yuji
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Kuge Yuji
Department Of Nuclear Medicine Graduate School Of Medicine Hokkaido University
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Saji Hideo
Department Of Cardiology Matsushita Memorial Hosipital
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Ogawa Yuki
Department Of Anatomy Tokyo Medical University
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Temma Takashi
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto University
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Sano Kohei
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto University
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Ogawa Yuki
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
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Sano Kohei
Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University
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