{"created":"2023-05-15T15:01:04.661888+00:00","id":82856,"links":{},"metadata":{"_buckets":{"deposit":"94cd4c03-17eb-4669-8a74-aabd5a402ebe"},"_deposit":{"created_by":1,"id":"82856","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"82856"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00082856","sets":["10:29"]},"author_link":["950400","950402","950403","950406","950401","950405","950397","950399","950404","950398"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2021-05-17","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Objectives: D-peptides are hyper-resistant to proteolytic degradation in L-homochiral living\nsubjects, making them remarkedly increased gut, blood plasma, and intracellular half-lives.\nD-peptides are theoretically ideal drug candidates, however, the potential of D-peptides in\nradiopharmaceuticals is rarely explored. Recently, a D-dodecapeptide antagonist (DPA) identified\nby mirror-image phage display revealed high efficacy to block the programmed death-ligand 1\n(PD-L1)/programmed death 1 (PD-1) interaction in animal models. In this work, we report the\nradiolabeling of DPA with 68Ga and study its metabolism and target engagement in tumor-bearing\nmice using PET. Methods: The PD-L1 protein expression in the human glioblastoma U87MG cell\nline was analyzed by flow cytometry and immunofluorescence imaging. The stability of [68Ga]DPA\nin saline and mouse serum was examined by radio HPLC and TLC. The cellular uptake of\n[68Ga]DPA into U87MG cells was measured at 15, 30, 60, and 120 min after co-incubation. For\nPET imaging, we inoculated 1×106 U87MG cells to the left flank of Balb/c nude mice\nsubcutaneously. When the tumors grow to ̴100 mm3 at 7 days after inoculation, mice were injected\nwith [68Ga]DPA (0.5 mCi per mouse) intravenously. Dynamic PET was performed from 0-60 min\npostinjection. To comprehensively profile the in vivo distribution of the tracer, ex vivo distribution\nwas carried out in Balb/c nude mice bearing U87MG tumors. Mice were sacrificed at 5, 30, 60, and\n120 min postinjection of the tracer (0.05 mCi per mouse). The tumor and organs were harvested and\nsubjected to gamma counter measurement. Based on the ex vivo biodistribution data, we calculated\nthe tumor to blood, tumor to liver, and tumor to muscle ratios. As a PD-L1 negative control, we also\nperformed PET imaging in Bon-1 tumor-bearing Balb/c nude mice. Finally, the PD-L1 expression\nlevel in U87MG and Bon-1 tumor tissue was immunohistologically stained and compared. Results:\nThe U87G cells were detected with approximately 60% subpopulation that express PD-L1 protein.\nThe uptake of the tracer by U87MG cells showed a time-dependent manner and increased from\n2%AD at 15 min of co-incubation to 4%AD at 120 min of co-incubation. Whole-body PET imaging\nshowed substantial [68Ga]DPA accumulation in U87MG tumors at 30 and 60 min postinjection. The\nhighest radioactivity appeared in the kidney and bladder, and non-striking radioactivity was noticed\nin other tissues, such as the liver and lung. Ex vivo biodistribution data verified the observation in\nthe PET study. The washout of the tracers from nonspecific organs such as blood, liver, and muscle\nwas significantly faster than that in the tumor, indicating PD-L1 specific retention in the U87MG\ntumor. The optimum image contrast was achieved at 60 min postinjection. Immunohistological\nanalysis revealed obvious PD-L1 expression in U87MG tumors but rare of that in Bon-1 tumors.\nConclusions: We have successfully labeled the DPA with 68Ga. The in vivo profile of [68Ga]DPA\nsuggested it a potential radiotracer for PD-L1 visualization. Our study paves the way for exploiting\nD-peptides as radiopharmaceuticals to manage cancer, both as PET tracers and radiotheranostics\nagents. Acknowledgement: We thank the financial support from the JSPS KAKENHI grant no.\n19K17156.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"eSRS","subitem_description_type":"Other"}]},"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":"Kuan, Hu"}],"nameIdentifiers":[{"nameIdentifier":"950397","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Lin, Xie"}],"nameIdentifiers":[{"nameIdentifier":"950398","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masayuki, Hanyu"}],"nameIdentifiers":[{"nameIdentifier":"950399","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"950400","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"950401","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kuan, Hu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"950402","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Lin, Xie","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"950403","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masayuki, Hanyu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"950404","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"950405","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"950406","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":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"PET imaging of PD-L1 overexpressing tumors with a 68Ga labeled D-dodecapeptide","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"PET imaging of PD-L1 overexpressing tumors with a 68Ga labeled D-dodecapeptide"}]},"item_type_id":"10005","owner":"1","path":["29"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-05-06"},"publish_date":"2021-05-06","publish_status":"0","recid":"82856","relation_version_is_last":true,"title":["PET imaging of PD-L1 overexpressing tumors with a 68Ga labeled D-dodecapeptide"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:09:19.895600+00:00"}