Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors

Temma, Takashi; Sano, Kohei; Kuge, Yuji; Kamihashi, Junko; Takai, Nobuhiko; Ogawa, Yuki; Saji, Hideo

doi:10.1248/bpb.32.1272

Cited by 27 publications

(36 citation statements)

References 30 publications

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“…MTl-MMP expressed on the tumor cell surface activates pro-MMP to exacerbate the malignancy and could be a powerful indicator of distant metastasis of gastric cancer. Specific downregulation of MTl-MMP expression causes significant inhibition of the migration and invasion oftumor cells, and anti-MTl-MMP mAb is a promising probe for future diagnosis oftumors by nuclear medical imaging (25,26). In our study, EP inhibited growth and metastasis of gastric cancer and decreased the expression of VEGF and MTl-MMP, suggesting that EP might inhibit tumor growth and metastasis through downregulation of VEGF and MTl-MMP expression.…”

Section: Discussionsupporting

confidence: 51%

Therapeutic Effects of Ethyl Pyruvate on Tumor Growth and Metastasis in a Severe Combined Immunodeficiency Mouse Orthotopic Implantation Model

Zhang

Zhou

et al. 2012

Eur J Inflamm

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Ethyl pyruvate (EP) has been shown to have significant anti-inflammatory activities. Here, we explore the therapeutic effects of EP administration on tumor growth and metastasis in orthotopic implantation human gastric cancer models in severe combined immunodeficiency (SCID) mice. After SCID mice were treated with EP, the tumor growth and liver metastasis from gastric cancer were investigated and its possible molecular mechanisms were further studied. As a result, it was found that EP could inhibit tumor growth and liver metastasis of gastric cancer, and reduce tumor Iymphangiogenesis indicated by lymphatic microvessel density (LVD) in gastric cancer and metastatic liver tumor. Also, EP decreased the expression of high mobility group box-Bl (HMGBl), receptor for advanced glycation endproducts (RAGE), vascular endothelial growth factor (VEGF) and membrane type-l matrix metalloprotease (MTI-MMP) in gastric cancer and metastatic liver tumor, but it exerted no effect on expression of nuclear factor-kappa B (NF-KB). Taken together, we suggest that the new application of EP could be a therapeutic option in the treatment of gastric cancer and metastatic liver tumor.

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Section: Discussionsupporting

confidence: 51%

Therapeutic Effects of Ethyl Pyruvate on Tumor Growth and Metastasis in a Severe Combined Immunodeficiency Mouse Orthotopic Implantation Model

Zhang

Zhou

et al. 2012

Eur J Inflamm

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“…The effectiveness of this pre-targeting method (streptavidinylated anti-MT1-MMP mAb and 123/125 I-IBB) was validated since significantly higher T/B ratios were achieved during the first hours after administration than had been observed in our previous study using a directly labeled antibody, 8) and SPECT imaging clearly visualized tumor tissues in vivo. It should be emphasized that in vivo imaging of MT1-MMP relevant to the malignancy of tumors was achieved in this study.…”

Section: Discussionmentioning

confidence: 93%

“…It should be stressed that chest organs such as the lungs and heart, and the liver were not visualized, which indicates the potential of this method for adequate imaging of breast tumors expressing MT1-MMP. In addition, preliminary Western blotting analysis using lysates from human breast cancer cells (MDA-MB-231) detected a high level of human MT1-MMP expression, 8) suggesting that this method may be useful in a clinical setting. We are currently investigating the effectiveness of this pre-targeting method across a variety of tumor cells that differently express MT1-MMP.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of MT1-MMP in FM3A cells and tumor tissues was confirmed by western blotting and immunohistochemistry. 8) Synthesis of Biotinylated Anti-MT1-MMP mAb Anti-MT1-MMP mAb (113-5B7, Daiichi Fine Chemical Co., Japan), a purified mouse monoclonal IgG 3 to an oligopeptide, residues 319 to 333 of human MT1-MMP numbered from the signal peptide, was used for experiments after purification with a HiTrap rProtein A column (GE Healthcare, U.K.). Since the amino acid sequence of the MT1-MMP protein is highly conserved among species including mouse, rat, rabbit, and human, 16) this antibody can cross-react with mouse as well as human MT1-MMP.…”

Section: Cell Lines and Animal Modelsmentioning

confidence: 99%

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Radioimmunodetection of Membrane Type-1 Matrix Metalloproteinase Relevant to Tumor Malignancy with a Pre-targeting Method

Sano

Temma

Kuge

et al. 2010

Biological & Pharmaceutical Bulletin

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Tumor malignancy is closely associated with the poor prognosis in cancer patients. Thus, accurate and sensitive diagnosis for detecting the tumor malignancy is required to provide the optimal therapeutic regimen to the patients. Nuclear medical techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive and have the potential to provide sensitive diagnoses by detecting gamma rays emitted from a radiolabeled probe injected into the body. Thus, a radiolabeled probe targeted to a biological molecule relevant to tumor malignancy can be a useful tool for detecting the malignant tumors.Matrix metalloproteinases (MMPs), classified as secreted MMPs and membrane-associated MMPs (membrane type MMPs, MT-MMPs) based on their structures, 1) play important roles in tumor growth, invasion, and metastasis by degrading most of the components in the extracellular matrix. 2)Membrane type-1 MMP (MT1-MMP) in particular is considered to be closely associated with tumor malignancy. Indeed, recent studies have shown that MT1-MMP activates MMP-2, an effector protease that operates downstream of MT1-MMP. 1,[3][4][5][6] In addition, expression of MT1-MMP is localized to tumor tissues 1) and increases in the early stages of tumorigenesis.7) Thus, MT1-MMP is a potential target for imaging malignant tumors at an early phase in their development.Recently, we proposed 99m Tc-labeled anti-MT1-MMP monoclonal immunoglobulin (IgG) ( 99m Tc-anti-MT1-MMP monoclonal antibody (mAb)) as a novel MT1-MMP probe and demonstrated its effectiveness for evaluating the malignancy of breast tumors in rodent models. 8) However, the blood clearance of 99m Tc-anti-MT1-MMP mAb was not fast enough to obtain a high tumor to blood (T/B) ratio, an indicator of availability of radiotracer for in vivo imaging, during the first hours following administration. The T/B ratio remained low at 48 h post-injection, which prevents the achievement of MT1-MMP imaging in vivo. For future clinical applications, this probe should be modified to improve the MT1-MMP imaging sensitivity and to provide earlier post-injection imaging.For this purpose, we planed to use a pre-targeting method combined with the anti-MT1-MMP mAb. The pre-targeting method, extensively studied in the field of radioimmunotherapy, can provide selective accumulation of radioactivity to the targeted organ and a high signal-to-noise (S/N) ratio during the first hours following administration.9,10) Recently, publications have reported that the pre-targeting method, utilizing an interaction between bispecific antibodies and haptens, is applicable to in vivo molecular imaging.11,12) Here, we exploited a streptavidin-biotin system possessing high affinity (K d ϭ10 Ϫ15 M) 13) for in vivo binding of pre-and postadministered compounds and applied this pre-targeting method to MT1-MMP imaging.This study sought to determine the effectiveness of a pretargeting protocol (streptavidinylated anti-MT1-MMP mAb and radiolabeled biotin) for MT1-MMP imaging shortly afte...

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“…After allowing sufficient time for POS to degrade in normal tissues, We also developed probes using anti-MT1-MMP antibody or its reduced-molecular-weight form for the target recognition unit and succeeded in imaging of MT1-MMP. [46][47][48][49][50][51] In addition, we performed research on structure-activity-distribution rela- tions of an asymmetric urea compound that binds to prostatespecific membrane antigen (PSMA) expressed in prostate cancer cell membrane, and developed a nuclear medical molecular imaging probe for PSMA-positive tumor. [52][53][54] We are currently preparing a clinical study using this probe.…”

Section: Molecular Imaging Of Tumorsmentioning

confidence: 99%

<i>In Vivo</i> Molecular Imaging

Saji

2017

Biological & Pharmaceutical Bulletin

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In vivo molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Among the methodologies used in in vivo molecular imaging, two methodologies are of great interest from the view of high sensitivity. One is nuclear medical imaging, and distribution and kinetics of a radiolabeled molecular probe are measured using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The other is optical molecular imaging, and distribution and kinetics of a fluorescent probe are measured using a fluorescent imaging instrument. In this review, the development of imaging probes for these two methodologies is briefly discussed. In nuclear medical molecular imaging, based on structure-activity-biodistribution relationship studies for small molecule and the concept of "functional unit-binding multifunctional molecular probe" containing 3 functional units (target recognition unit, signal-releasing unit, linker unit) for peptides and proteins, we developed radiolabeled probes with high and specific accumulation to the target for neuroreceptors, β-amyloid plaques, and tau aggregates in the brain, tumors, atherosclerotic plaques, pancreatic β-cell, myocardial sympathetic nerves, and so on. We also discuss the progression of molecular imaging toward therapy (radiotheranotics). In in vivo optical molecular imaging, taking into account the characteristics of optical imaging, we designed tumor-specific optical imaging probes with characteristic imaging mechanism, including near-infrared (NIR) fluorescent probes and activatable probes. Furthermore, we developed a photoacoustic imaging probe, which enables highly sensitive and high-resolution imaging in deep tissues.

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Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors

Cited by 27 publications

References 30 publications

Therapeutic Effects of Ethyl Pyruvate on Tumor Growth and Metastasis in a Severe Combined Immunodeficiency Mouse Orthotopic Implantation Model

Therapeutic Effects of Ethyl Pyruvate on Tumor Growth and Metastasis in a Severe Combined Immunodeficiency Mouse Orthotopic Implantation Model

Radioimmunodetection of Membrane Type-1 Matrix Metalloproteinase Relevant to Tumor Malignancy with a Pre-targeting Method

<i>In Vivo</i> Molecular Imaging

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