WEKO3
アイテム
{"_buckets": {"deposit": "05c49da8-a064-498e-96a5-9d0aacd80858"}, "_deposit": {"created_by": 1, "id": "45107", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "45107"}, "status": "published"}, "_oai": {"id": "oai:repo.qst.go.jp:00045107", "sets": ["1"]}, "author_link": ["447935", "447945", "447947", "447936", "447941", "447939", "447940", "447946", "447942", "447948", "447937", "447944", "447943", "447938"], "item_8_biblio_info_7": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2007-07", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "5", "bibliographicPageEnd": "510", "bibliographicPageStart": "503", "bibliographicVolumeNumber": "34", "bibliographic_titles": [{"bibliographic_title": "Nuclear Medicine and Biology"}]}]}, "item_8_description_5": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Since elevated levels of gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are associated with a poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging. In the present study, a cyclic decapeptide, cCTTHWGFTLC (CTT), was selected as a mother compound because of its selective inhibitory activity toward gelatinases. For imaging gelatinase activity in tumors, we designed a CTT-based radiopharmaceutical taking into consideration that (1) the HWGF motif of the peptide is important for the activity, (2) hydrophilic radiolabeled peptides show low-level accumulation in the liver and (3) an increase in the negative charge of radiolabeled peptides is effective in reducing renal accumulation. Thus, a highly hydrophilic and negatively charged radiolabel, indiun-111-diethylenetriaminepentaacetic acid ((111)In-DTPA), was attached to an N-terminal residue distant from the HWGF motif ((111)In-DTPA-CTT). In MMP-2 inhibition assays, In-DTPA-CTT significantly inhibited the proteolytic activity in a concentration-dependent fashion. When injected into normal mice, (111)In-DTPA-CTT showed low levels of radioactivity in the liver and kidney. A comparison of the pharmacokinetic characteristics of (111)In-DTPA-CTT with those of other CTT derivatives having different physicochemical properties revealed that the increase in hydrophilicity and negative charge caused by the conjugation of (111)In-DTPA reduced levels of radioactivity in the liver and kidney. In tumor-bearing mice, a significant correlation was observed between the accumulation in the tumor as well as tumor-to-blood ratio of (111)In-DTPA-CTT and gelatinase activity. These findings support the validity of the chemical design of (111)In-DTPA-CTT for reducing accumulation in nontarget tissues and maintaining the inhibitory activity of the mother compound. Furthermore, (111)In-DTPA-CTT derivatives would be potential radiopharmaceuticals for the imaging of gelatinase activity in metastatic tumors in vivo.", "subitem_description_type": "Abstract"}]}, "item_8_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0969-8051", "subitem_source_identifier_type": "ISSN"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "metadata only access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_14cb"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Hanaoka, Hirofumi"}], "nameIdentifiers": [{"nameIdentifier": "447935", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Mukai, Takahiro"}], "nameIdentifiers": [{"nameIdentifier": "447936", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Habashita, Sayo"}], "nameIdentifiers": [{"nameIdentifier": "447937", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Asano, Daigo"}], "nameIdentifiers": [{"nameIdentifier": "447938", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ogawa, Kazuma"}], "nameIdentifiers": [{"nameIdentifier": "447939", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kuroda, Yoshihiro"}], "nameIdentifiers": [{"nameIdentifier": "447940", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Akizawa, Hiromichi"}], "nameIdentifiers": [{"nameIdentifier": "447941", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "IIda, Yasuhiko"}], "nameIdentifiers": [{"nameIdentifier": "447942", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Endou, Keigo"}], "nameIdentifiers": [{"nameIdentifier": "447943", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Saga, Tsuneo"}], "nameIdentifiers": [{"nameIdentifier": "447944", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Saji, Hideo"}], "nameIdentifiers": [{"nameIdentifier": "447945", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "秋澤 宏行", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "447946", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "遠藤 啓吾", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "447947", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "佐賀 恒夫", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "447948", "nameIdentifierScheme": "WEKO"}]}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors.", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors."}]}, "item_type_id": "8", "owner": "1", "path": ["1"], "permalink_uri": "https://repo.qst.go.jp/records/45107", "pubdate": {"attribute_name": "公開日", "attribute_value": "2008-03-04"}, "publish_date": "2008-03-04", "publish_status": "0", "recid": "45107", "relation": {}, "relation_version_is_last": true, "title": ["Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors."], "weko_shared_id": -1}
Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors.
https://repo.qst.go.jp/records/45107
https://repo.qst.go.jp/records/4510720092b18-a60c-43a2-81d9-f155fefabb60
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2008-03-04 | |||||
タイトル | ||||||
タイトル | Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Hanaoka, Hirofumi
× Hanaoka, Hirofumi× Mukai, Takahiro× Habashita, Sayo× Asano, Daigo× Ogawa, Kazuma× Kuroda, Yoshihiro× Akizawa, Hiromichi× IIda, Yasuhiko× Endou, Keigo× Saga, Tsuneo× Saji, Hideo× 秋澤 宏行× 遠藤 啓吾× 佐賀 恒夫 |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Since elevated levels of gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are associated with a poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging. In the present study, a cyclic decapeptide, cCTTHWGFTLC (CTT), was selected as a mother compound because of its selective inhibitory activity toward gelatinases. For imaging gelatinase activity in tumors, we designed a CTT-based radiopharmaceutical taking into consideration that (1) the HWGF motif of the peptide is important for the activity, (2) hydrophilic radiolabeled peptides show low-level accumulation in the liver and (3) an increase in the negative charge of radiolabeled peptides is effective in reducing renal accumulation. Thus, a highly hydrophilic and negatively charged radiolabel, indiun-111-diethylenetriaminepentaacetic acid ((111)In-DTPA), was attached to an N-terminal residue distant from the HWGF motif ((111)In-DTPA-CTT). In MMP-2 inhibition assays, In-DTPA-CTT significantly inhibited the proteolytic activity in a concentration-dependent fashion. When injected into normal mice, (111)In-DTPA-CTT showed low levels of radioactivity in the liver and kidney. A comparison of the pharmacokinetic characteristics of (111)In-DTPA-CTT with those of other CTT derivatives having different physicochemical properties revealed that the increase in hydrophilicity and negative charge caused by the conjugation of (111)In-DTPA reduced levels of radioactivity in the liver and kidney. In tumor-bearing mice, a significant correlation was observed between the accumulation in the tumor as well as tumor-to-blood ratio of (111)In-DTPA-CTT and gelatinase activity. These findings support the validity of the chemical design of (111)In-DTPA-CTT for reducing accumulation in nontarget tissues and maintaining the inhibitory activity of the mother compound. Furthermore, (111)In-DTPA-CTT derivatives would be potential radiopharmaceuticals for the imaging of gelatinase activity in metastatic tumors in vivo. | |||||
書誌情報 |
Nuclear Medicine and Biology 巻 34, 号 5, p. 503-510, 発行日 2007-07 |
|||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0969-8051 |