{"created":"2023-07-27T06:55:05.036064+00:00","id":50752,"links":{},"metadata":{"_buckets":{"deposit":"c65340b6-8423-424c-9dda-18c83508eca9"},"_deposit":{"created_by":18,"id":"50752","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"50752"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00050752","sets":["2812:2813:2829"]},"author_link":["85518","40"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2005-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"41p.","bibliographicVolumeNumber":"2002-2004","bibliographic_titles":[{"bibliographic_title":"平成16(2004)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"2004 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"近年、精神疾患や痴呆等の脳内神経変性疾患の早期検出が望まれており、そのためには、神経変性過程において、神経細胞のどの機能変化が先行指標となり得るか、即ち変性過程の早期に起こり発症に至る神経細胞の機能変化は何かを明らかにする必要がある。本研究では、脳内神経変性疾患モデル動物による発症過程において、神経機能との関わりが深い放射性診断薬を用いてその機能変化を評価し、病態発症との相関を検討した。\nパーキンソン病の早期診断を目的とし、6-ヒドロキシドーパミンによる偏側神経破壊パーキンソン病モデルラットを用いて、発症過程にみられる脳内ドーパミン神経機能変化を、ドーパミンレセプターリガンドや、ドーパミンの前駆物質であるドーパ誘導体等のPET製剤投与により解析し、画像化した。その結果、大脳皮質や小脳では、無処置側に対する処置側の集積比に顕著な変化は認められなかった。線条体における集積は、D1レセプターは急性期には変化せず、発症期に微増した。D2レセプターでは急性期から顕著な増加がみられ、発症期にはさらに増加した。ドーパミン動態では急性期に低下し、発症期に回復傾向が認められた。これらの変化は、行動薬理試験や免疫染色の結果とも相関しており、発症過程の先行指標になり得ると考えられた。\nまた、SPECTへの応用を計画し、我々がこれまでに開発したアミノ酸膜輸送機能診断薬や、ドーパ脱炭酸酵素活性を反映するアミノ酸誘導体を母体構造とした新規放射性ヨウ素標識薬剤を用いて同様に評価した。ドーパ脱炭酸酵素活性では個体間の差が大きかったが、アミノ酸膜輸送機能、ドーパ脱炭酸酵素機能ともに、発症期に低下する傾向がみられた。特にドーパ脱炭酸酵素活性では急性期より低下する傾向が認められ、早期診断への応用が期待された。\n以上より、特に処置後早期の急性期より神経機能変化を検出し得たことから、これらの神経機能を指標としたパーキンソン病の早期画像診断の可能性が示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"We studied the PET tracer distributions of ligands for dopamine D_1 receptors ([^<11>C]SCH23390) and D_2 receptors ([^<11>C]raclopride) and of the dopamine precursor analog 6-[^<18>F]fluoro-L-3,4-dihydroxyphenylalanine ([^<18>F]FDOPA) in the brain after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The number of methamphetamine-induced rotation was higher at 14 days than that at 3 days following the 6-OHDA lesions. The brains of 6-OHDA treated rats were analyzed by tissue dissection following i.v.bolus of each tracer at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [^<11>C]Raclopride, but not [^<11>C]SCH23390,showed a higher accumulation in the striatum on the lesion side compared with that on the non-lesioned (intact) side both 3 days and 3 weeks postlesion. On the other hand, a lower accumulation of [^<18>F]FDOPA was found in the striatum on the lesion side 3 days postlesion, and both in the striatum and cerebral cortex on the lesion side 3 weeks postlesion. Our studies demonstrate that an increase in [^<11>C]raclopride and a decrease in [^<18>F]FDOPA uptake in the denervated striatum is evident even at 3 days following the 6-OHDA lesions when the degree of methamphetamine-induced rotation is not established. Therefore the combination of a D_2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.\nFor SPECT application, radioiodinated derivatives of L-tyrosine, dopamine biosynthesis precursor, were evaluated as diagnosis agents for early detection of neurodegeneration. 3-[^<123>I]iodo-α-methyl-L-tyrosine (I-IMT) and 3-[^<123>I]iodo-α-difluoromethyl-tyrosine methyl ester (I-FTM) were selected as SPECT imaging agents for cerebral amino acid transpoter and dopa decarboxylase (DDC) activity. In the biodistribution study, I-IMT accumulation in the striatum on the lesion side 3 days postlesion increased, then decreased in 2 weeks postlesion, compared with the intact side. On the other hand, I-FTM showed a lower accumulation in the striatum on the lesion side compared with that on the intact side both 3 days and 2 weeks postlesion. It shows that I-FTM, with an affinity to the final enzyme of dopamine biosynthesis, was sensitive for detection of neurodegeneration in acute stage. Thus, both I-IMT and I-FTM may be new candidates of radiopharmaceuticals that can be useful in assessing function of cerebral dopaminergic neuron.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:14370273, 研究期間(年度):2002-2004","subitem_description_type":"Other"},{"subitem_description":"出典：「脳内神経変性疾患の早期検出を可能にする新規放射性診断薬の開発に関する研究」研究成果報告書　課題番号14370273\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00057060","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医薬保健研究域保健学系"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=30204663"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=30204663","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370273/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370273/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14370273/143702732004kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14370273/143702732004kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-02-20"}],"displaytype":"detail","filename":"ME-PR-KAWAI-K-keken 2006-41p.pdf","filesize":[{"value":"1.5 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-KAWAI-K-keken 2006-41p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/50752/files/ME-PR-KAWAI-K-keken 2006-41p.pdf"},"version_id":"18a49007-d81a-4353-b838-249df61a03d8"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"脳内神経変性疾患の早期検出を可能にする新規放射性診断薬の開発に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"脳内神経変性疾患の早期検出を可能にする新規放射性診断薬の開発に関する研究"},{"subitem_title":"Development of novel radiopharmaceuticals for early stage diagnosis of cerebral neurodegeneration","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2829"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-02-20"},"publish_date":"2020-02-20","publish_status":"0","recid":"50752","relation_version_is_last":true,"title":["脳内神経変性疾患の早期検出を可能にする新規放射性診断薬の開発に関する研究"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:28:43.573111+00:00"}