WEKO3
アイテム
{"_buckets": {"deposit": "18938b12-902e-4a4c-9cc7-bec3577cf14c"}, "_deposit": {"created_by": 1, "id": "71871", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "71871"}, "status": "published"}, "_oai": {"id": "oai:repo.qst.go.jp:00071871", "sets": ["28"]}, "author_link": ["707761", "707755", "707759", "707771", "707769", "707762", "707757", "707753", "707772", "707760", "707766", "707763", "707765", "707768", "707770", "707756", "707764", "707767", "707758", "707754"], "item_10005_date_7": {"attribute_name": "発表年月日", "attribute_value_mlt": [{"subitem_date_issued_datetime": "2015-11-09", "subitem_date_issued_type": "Issued"}]}, "item_10005_description_5": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Objectives: 1-Methyl-tryptophan (1MTrp) is known as a specific inhibitor targeting the immune- checkpoint protein indoleamine-2,3-dioxygenase, in two stereoisomers of levorotary (L) and dextrorotary (D) (1). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy (2). As a first step to disentangle the potential and explore the possibility of pharmacokinetic imaging in immunotherapy, we here developed two novel radioprobes, 1-N-[11C]methyl-L- and -D-tryptophan ([11C]L-1MTrp and [11C]D-1-MTrp), without modifying the chemical structures of the two isomers, and delineated their pharmacokinetic imaging in whole body. \nMethods: [11C]L-1MTrp and [11C]D-1MTrp were synthesized by reaction of the corresponding Boc-Trp-OEt with [11C]CH3I at 80 °C for 5 min, followed by deprotection with 2 N HCl at 100 °C for 5 min. The pharmacokinetics of the L and D isomers were tracked using dynamic PET/CT scans and biodistribution study after the radioprobes injection.\nResults: [11C]L-1MTrp and [11C]D-1MTrp were obtained with radiochemical yields of 47 ± 6.3% (decay-corrected, based on [11C]CO2), a radiochemical purity of \u003e 98%, specific activity of 47130 GBq/μmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for [11C]L-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for [11C]D-1MTrp, it was observed in the kidney (Fig. 1). Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. \nConclusion: Both [11C]L-1MTrp and [11C]D-1MTrp are therefore useful PET probes for delineating the distribution and action of the checkpoint inhibitor 1MTrp in vivo. This study represents the first step toward using whole-body and real-time insight to disentangle the antitumor potential of the two stereoisomers of 1MTrp, and it can facilitate the development of 1MTrp immunotherapy.", "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": "Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry", "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": "Xie, Lin"}], "nameIdentifiers": [{"nameIdentifier": "707753", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Maeda, Jun"}], "nameIdentifiers": [{"nameIdentifier": "707754", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kumata, Katsushi"}], "nameIdentifiers": [{"nameIdentifier": "707755", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yui, Joji"}], "nameIdentifiers": [{"nameIdentifier": "707756", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Zhang, Yiding"}], "nameIdentifiers": [{"nameIdentifier": "707757", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hatori, Akiko"}], "nameIdentifiers": [{"nameIdentifier": "707758", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nengaki, Nobuki"}], "nameIdentifiers": [{"nameIdentifier": "707759", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Wakizaka, Hidekatsu"}], "nameIdentifiers": [{"nameIdentifier": "707760", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Fujinaga, Masayuki"}], "nameIdentifiers": [{"nameIdentifier": "707761", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Zhang, Ming-Rong"}], "nameIdentifiers": [{"nameIdentifier": "707762", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "謝 琳", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707763", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "前田 純", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707764", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "熊田 勝志", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707765", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "由井 譲二", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707766", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "張 一鼎", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707767", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "羽鳥 晶子", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707768", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "念垣 信樹", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707769", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "脇坂 秀克", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707770", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "藤永 雅之", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707771", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "張 明栄", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "707772", "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": "Development of 1-N-[11C]-Methyl-L- and -D-Tryptophan for Pharmacokinetic Imaging of the Immune Checkpoint Inhibitor 1-Methyl-Tryptophan", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Development of 1-N-[11C]-Methyl-L- and -D-Tryptophan for Pharmacokinetic Imaging of the Immune Checkpoint Inhibitor 1-Methyl-Tryptophan"}]}, "item_type_id": "10005", "owner": "1", "path": ["28"], "permalink_uri": "https://repo.qst.go.jp/records/71871", "pubdate": {"attribute_name": "公開日", "attribute_value": "2015-11-25"}, "publish_date": "2015-11-25", "publish_status": "0", "recid": "71871", "relation": {}, "relation_version_is_last": true, "title": ["Development of 1-N-[11C]-Methyl-L- and -D-Tryptophan for Pharmacokinetic Imaging of the Immune Checkpoint Inhibitor 1-Methyl-Tryptophan"], "weko_shared_id": -1}
Development of 1-N-[11C]-Methyl-L- and -D-Tryptophan for Pharmacokinetic Imaging of the Immune Checkpoint Inhibitor 1-Methyl-Tryptophan
https://repo.qst.go.jp/records/71871
https://repo.qst.go.jp/records/718717a696ad5-6f22-4d44-93f5-581743cdd8e0
Item type | 会議発表用資料 / Presentation(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2015-11-25 | |||||
タイトル | ||||||
タイトル | Development of 1-N-[11C]-Methyl-L- and -D-Tryptophan for Pharmacokinetic Imaging of the Immune Checkpoint Inhibitor 1-Methyl-Tryptophan | |||||
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_c94f | |||||
資源タイプ | conference object | |||||
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 |
Xie, Lin
× Xie, Lin× Maeda, Jun× Kumata, Katsushi× Yui, Joji× Zhang, Yiding× Hatori, Akiko× Nengaki, Nobuki× Wakizaka, Hidekatsu× Fujinaga, Masayuki× Zhang, Ming-Rong× 謝 琳× 前田 純× 熊田 勝志× 由井 譲二× 張 一鼎× 羽鳥 晶子× 念垣 信樹× 脇坂 秀克× 藤永 雅之× 張 明栄 |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Objectives: 1-Methyl-tryptophan (1MTrp) is known as a specific inhibitor targeting the immune- checkpoint protein indoleamine-2,3-dioxygenase, in two stereoisomers of levorotary (L) and dextrorotary (D) (1). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy (2). As a first step to disentangle the potential and explore the possibility of pharmacokinetic imaging in immunotherapy, we here developed two novel radioprobes, 1-N-[11C]methyl-L- and -D-tryptophan ([11C]L-1MTrp and [11C]D-1-MTrp), without modifying the chemical structures of the two isomers, and delineated their pharmacokinetic imaging in whole body. Methods: [11C]L-1MTrp and [11C]D-1MTrp were synthesized by reaction of the corresponding Boc-Trp-OEt with [11C]CH3I at 80 °C for 5 min, followed by deprotection with 2 N HCl at 100 °C for 5 min. The pharmacokinetics of the L and D isomers were tracked using dynamic PET/CT scans and biodistribution study after the radioprobes injection. Results: [11C]L-1MTrp and [11C]D-1MTrp were obtained with radiochemical yields of 47 ± 6.3% (decay-corrected, based on [11C]CO2), a radiochemical purity of > 98%, specific activity of 47130 GBq/μmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for [11C]L-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for [11C]D-1MTrp, it was observed in the kidney (Fig. 1). Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. Conclusion: Both [11C]L-1MTrp and [11C]D-1MTrp are therefore useful PET probes for delineating the distribution and action of the checkpoint inhibitor 1MTrp in vivo. This study represents the first step toward using whole-body and real-time insight to disentangle the antitumor potential of the two stereoisomers of 1MTrp, and it can facilitate the development of 1MTrp immunotherapy. |
|||||
会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry | |||||
発表年月日 | ||||||
日付 | 2015-11-09 | |||||
日付タイプ | Issued |