Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors
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 a...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2009/07/01, Vol.32(7), pp.1272-1277 |
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| creator | Temma, Takashi Sano, Kohei Kuge, Yuji Kamihashi, Junko Takai, Nozomi Ogawa, Yuki Saji, Hideo |
| description | 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 |
| doi_str_mv | 10.1248/bpb.32.1272 |
| format | Article |
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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.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.32.1272</identifier><identifier>PMID: 19571397</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - chemistry ; Biomarkers, Tumor - analysis ; Blotting, Western ; Breast Neoplasms - diagnostic imaging ; Breast Neoplasms - enzymology ; Breast Neoplasms - pathology ; breast tumor ; Cell Line, Tumor ; Diagnostic Techniques, Radioisotope ; Female ; Hydrazines - administration & dosage ; Hydrazines - chemistry ; Matrix Metalloproteinase 14 - analysis ; membrane type-1 matrix metalloproteinase ; Mice ; Mice, Inbred C3H ; Neoplasm Transplantation ; Nicotinic Acids - administration & dosage ; Nicotinic Acids - chemistry ; non-invasive imaging ; Radionuclide Imaging ; Rats ; Rats, Sprague-Dawley ; single photon emission computed tomography ; Technetium - administration & dosage ; Technetium - chemistry</subject><ispartof>Biological and Pharmaceutical Bulletin, 2009/07/01, Vol.32(7), pp.1272-1277</ispartof><rights>2009 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-5e86d9d3b55584d6a2ff5f4d0ba43bfe36d4513d5d122ad8c13b1cb1144e096d3</citedby><cites>FETCH-LOGICAL-c587t-5e86d9d3b55584d6a2ff5f4d0ba43bfe36d4513d5d122ad8c13b1cb1144e096d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19571397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Temma, Takashi</creatorcontrib><creatorcontrib>Sano, Kohei</creatorcontrib><creatorcontrib>Kuge, Yuji</creatorcontrib><creatorcontrib>Kamihashi, Junko</creatorcontrib><creatorcontrib>Takai, Nozomi</creatorcontrib><creatorcontrib>Ogawa, Yuki</creatorcontrib><creatorcontrib>Saji, Hideo</creatorcontrib><title>Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>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.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Blotting, Western</subject><subject>Breast Neoplasms - diagnostic imaging</subject><subject>Breast Neoplasms - enzymology</subject><subject>Breast Neoplasms - pathology</subject><subject>breast tumor</subject><subject>Cell Line, Tumor</subject><subject>Diagnostic Techniques, Radioisotope</subject><subject>Female</subject><subject>Hydrazines - administration & dosage</subject><subject>Hydrazines - chemistry</subject><subject>Matrix Metalloproteinase 14 - analysis</subject><subject>membrane type-1 matrix metalloproteinase</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Neoplasm Transplantation</subject><subject>Nicotinic Acids - administration & dosage</subject><subject>Nicotinic Acids - chemistry</subject><subject>non-invasive imaging</subject><subject>Radionuclide Imaging</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>single photon emission computed tomography</subject><subject>Technetium - administration & dosage</subject><subject>Technetium - chemistry</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1rFDEYh4Modq2evEtA8CLT5nMyc7O0fhRaFFnPIZm8s86SSdYkI_a_N8uuFXrpJQl5H573TX4IvabkjDLRndudPeOsnhV7glaUC9VIRuVTtCI97ZqWyu4Evch5SwhRhPHn6IT2UlHeqxUKV_AbfNzNEAqOIzb4u3FT9MaCB4e_pWgBjzHhKygwlCls8C3MNpkAeH23g4biW1PS9KdeF-OrKcUCUzAZcAy15qdNMNW9XuaY8kv0bDQ-w6vjfop-fPq4vvzS3Hz9fH15cdMMslOlkdC1rnfcSik74VrDxlGOwhFrBLcj8NYJSbmTjjJmXDdQbulgKRUCSN86foreHbx1nF8L5KLnKQ_gfZ07Llm3Soj6A_RRkBHVt4p3FXz7ANzGJYX6CF279lxxpVSl3h-oIcWcE4x6l6bZpDtNid6npWtamjO9T6vSb47Oxc7g_rPHeCrw4QBsczEbuAdMKtPg4Z9MHZa98740_DRJQ-B_AY8apzM</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Temma, Takashi</creator><creator>Sano, Kohei</creator><creator>Kuge, Yuji</creator><creator>Kamihashi, Junko</creator><creator>Takai, Nozomi</creator><creator>Ogawa, Yuki</creator><creator>Saji, Hideo</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20090701</creationdate><title>Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors</title><author>Temma, Takashi ; Sano, Kohei ; Kuge, Yuji ; Kamihashi, Junko ; Takai, Nozomi ; Ogawa, Yuki ; Saji, Hideo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-5e86d9d3b55584d6a2ff5f4d0ba43bfe36d4513d5d122ad8c13b1cb1144e096d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Blotting, Western</topic><topic>Breast Neoplasms - diagnostic imaging</topic><topic>Breast Neoplasms - enzymology</topic><topic>Breast Neoplasms - pathology</topic><topic>breast tumor</topic><topic>Cell Line, Tumor</topic><topic>Diagnostic Techniques, Radioisotope</topic><topic>Female</topic><topic>Hydrazines - administration & dosage</topic><topic>Hydrazines - chemistry</topic><topic>Matrix Metalloproteinase 14 - analysis</topic><topic>membrane type-1 matrix metalloproteinase</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Neoplasm Transplantation</topic><topic>Nicotinic Acids - administration & dosage</topic><topic>Nicotinic Acids - chemistry</topic><topic>non-invasive imaging</topic><topic>Radionuclide Imaging</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>single photon emission computed tomography</topic><topic>Technetium - administration & dosage</topic><topic>Technetium - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Temma, Takashi</creatorcontrib><creatorcontrib>Sano, Kohei</creatorcontrib><creatorcontrib>Kuge, Yuji</creatorcontrib><creatorcontrib>Kamihashi, Junko</creatorcontrib><creatorcontrib>Takai, Nozomi</creatorcontrib><creatorcontrib>Ogawa, Yuki</creatorcontrib><creatorcontrib>Saji, Hideo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Temma, Takashi</au><au>Sano, Kohei</au><au>Kuge, Yuji</au><au>Kamihashi, Junko</au><au>Takai, Nozomi</au><au>Ogawa, Yuki</au><au>Saji, Hideo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>32</volume><issue>7</issue><spage>1272</spage><epage>1277</epage><pages>1272-1277</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>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.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>19571397</pmid><doi>10.1248/bpb.32.1272</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - chemistry Biomarkers, Tumor - analysis Blotting, Western Breast Neoplasms - diagnostic imaging Breast Neoplasms - enzymology Breast Neoplasms - pathology breast tumor Cell Line, Tumor Diagnostic Techniques, Radioisotope Female Hydrazines - administration & dosage Hydrazines - chemistry Matrix Metalloproteinase 14 - analysis membrane type-1 matrix metalloproteinase Mice Mice, Inbred C3H Neoplasm Transplantation Nicotinic Acids - administration & dosage Nicotinic Acids - chemistry non-invasive imaging Radionuclide Imaging Rats Rats, Sprague-Dawley single photon emission computed tomography Technetium - administration & dosage Technetium - chemistry |
| title | Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors |
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