Radioimmunodetection of Membrane Type-1 Matrix Metalloproteinase Relevant to Tumor Malignancy with a Pre-targeting Method
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概要
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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.
- 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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ZHAO Songji
Department of Nuclear Medicine and Diagnostic Imaging, Kyoto University Graduate School of Medicine
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KUDO Takashi
Department of Radiology, Kinki University School of Medicine
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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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Zhao Songji
Department Of Nuclear Medicine And Diagnostic Imaging Kyoto University Graduate School Of Medicine
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Kudo Takashi
Department Of Clinical Neuroscience Psychiatry Graduate School Of Medicine Osaka University
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Saji Hideo
Department Of Cardiology Matsushita Memorial Hosipital
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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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Kudo Takashi
Department Of Anatomy And Embryology Faculty Of Medicine University Of Tsukuba
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Zhao Songji
Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido 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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