{"created":"2023-05-15T14:34:53.237807+00:00","id":45107,"links":{},"metadata":{"_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"],"pubdate":{"attribute_name":"公開日","attribute_value":"2008-03-04"},"publish_date":"2008-03-04","publish_status":"0","recid":"45107","relation_version_is_last":true,"title":["Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-16T00:07:36.253682+00:00"}