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To clarify\nwhether [11C]PBB3 binds to a-synuclein pathology,\nreactivity of PBB3 was assessed by in vitro fluorescence\nand autoradiographic labeling of brain sections\nfrom a-synucleinopathies patients.\nMethod: Of 10 pure Lewy body disease and 120 multiple\nsystem atrophy (MSA) cases in the Mayo Clinic\nbrain bank, we selected 3 Lewy body disease and 4\nMSA cases with a range of a-synuclein severity based\non the quantitative analysis of a-synuclein burden.\nPBB3 fluorescence labeling, double or single immunostaining\nfor a-synuclein and phospho-tau, Prussian blue\nstaining, and in vitro autoradiography with [11C]PBB3\nwere performed for these selected samples.\nResults: PBB3 fluorescence labeled various asynuclein\nlesions including Lewy bodies, Lewy neurites,\nspheroids, glial cytoplasmic inclusions, and neuronal\ncytoplasmic inclusions. Meanwhile, autoradiographic\nlabeling with [11C]PBB3 at 10nM demonstrated no significant\nbinding in Lewy body disease cases. In contrast,\nsignificant autoradiographic binding of [11C]PBB3\nto the striatopallidal fibers was found in 2 MSA cases,\nwhich had high densities of glial cytoplasmic inclusions\nwithout tau or iron deposits in this region.\nConclusions: Given that the maximum concentration of\n[11C]PBB3 in human PET scans is approximately 10 nM,\nthe present data imply that a-synuclein pathology in\nLewy body disease is undetectable by [11C]PBB3-PET,\nwhereas those in a subset of MSA cases with high densities\nof glial cytoplasmic inclusions could be captured\nby this radioligand. VC 2016 International Parkinson and\nMovement Disorder Society\nKey Words: Lewy body disease; multiple system\natrophy; a-synucleinopathy; PBB3; autoradiography", "subitem_description_type": "Abstract"}]}, "item_8_relation_13": {"attribute_name": "PubMed番号", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "28440890", "subitem_relation_type_select": "PMID"}}]}, "item_8_relation_14": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1002/mds.27013", "subitem_relation_type_select": "DOI"}}]}, "item_8_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0885-3185", "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": "Koga, Shunsuke"}], "nameIdentifiers": [{"nameIdentifier": "493268", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ono, Maiko"}], "nameIdentifiers": [{"nameIdentifier": "493269", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sahara, Naruhiko"}], "nameIdentifiers": [{"nameIdentifier": "493270", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Higuchi, Makoto"}], "nameIdentifiers": [{"nameIdentifier": "493271", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "W., Dickson Dennis"}], "nameIdentifiers": [{"nameIdentifier": "493272", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "小野 麻衣子", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "493273", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "佐原 成彦", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "493274", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "樋口 真人", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "493275", "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": "Fluorescence and Autoradiographic Evaluation of Tau PET Ligand PBB3 to α-Synuclein Pathology", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Fluorescence and Autoradiographic Evaluation of Tau PET Ligand PBB3 to α-Synuclein Pathology"}]}, "item_type_id": "8", "owner": "1", "path": ["1"], "permalink_uri": "https://repo.qst.go.jp/records/48945", "pubdate": {"attribute_name": "公開日", "attribute_value": "2018-05-11"}, "publish_date": "2018-05-11", "publish_status": "0", "recid": "48945", "relation": {}, "relation_version_is_last": true, "title": ["Fluorescence and Autoradiographic Evaluation of Tau PET Ligand PBB3 to α-Synuclein Pathology"], "weko_shared_id": -1}
Fluorescence and Autoradiographic Evaluation of Tau PET Ligand PBB3 to α-Synuclein Pathology
https://repo.qst.go.jp/records/48945
https://repo.qst.go.jp/records/48945ff7c9ffe-3ca0-48a5-8506-2f9559a83c61
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-05-11 | |||||
タイトル | ||||||
タイトル | Fluorescence and Autoradiographic Evaluation of Tau PET Ligand PBB3 to α-Synuclein Pathology | |||||
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 |
Koga, Shunsuke
× Koga, Shunsuke× Ono, Maiko× Sahara, Naruhiko× Higuchi, Makoto× W., Dickson Dennis× 小野 麻衣子× 佐原 成彦× 樋口 真人 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | ABSTRACT: Background: The tau PET ligand 2- ((1E,3E)-4-(6-([11C]methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol ([11C]PBB3) binds to a wide range of tau pathology; however, binding property of PBB3 to non-tau inclusions remains unknown. To clarify whether [11C]PBB3 binds to a-synuclein pathology, reactivity of PBB3 was assessed by in vitro fluorescence and autoradiographic labeling of brain sections from a-synucleinopathies patients. Method: Of 10 pure Lewy body disease and 120 multiple system atrophy (MSA) cases in the Mayo Clinic brain bank, we selected 3 Lewy body disease and 4 MSA cases with a range of a-synuclein severity based on the quantitative analysis of a-synuclein burden. PBB3 fluorescence labeling, double or single immunostaining for a-synuclein and phospho-tau, Prussian blue staining, and in vitro autoradiography with [11C]PBB3 were performed for these selected samples. Results: PBB3 fluorescence labeled various asynuclein lesions including Lewy bodies, Lewy neurites, spheroids, glial cytoplasmic inclusions, and neuronal cytoplasmic inclusions. Meanwhile, autoradiographic labeling with [11C]PBB3 at 10nM demonstrated no significant binding in Lewy body disease cases. In contrast, significant autoradiographic binding of [11C]PBB3 to the striatopallidal fibers was found in 2 MSA cases, which had high densities of glial cytoplasmic inclusions without tau or iron deposits in this region. Conclusions: Given that the maximum concentration of [11C]PBB3 in human PET scans is approximately 10 nM, the present data imply that a-synuclein pathology in Lewy body disease is undetectable by [11C]PBB3-PET, whereas those in a subset of MSA cases with high densities of glial cytoplasmic inclusions could be captured by this radioligand. VC 2016 International Parkinson and Movement Disorder Society Key Words: Lewy body disease; multiple system atrophy; a-synucleinopathy; PBB3; autoradiography |
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書誌情報 |
Movement Disorders 巻 32, 号 6, p. 884-892, 発行日 2017-04 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0885-3185 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 28440890 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1002/mds.27013 |