A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors

• 資料種別: 博士論文
• ISSN: 1838-7640
• タイトル: A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors
• 巻次・部編番号: 8 9
• 著者・編者: Fujimoto, Shota; Muguruma, Naoki; Okamoto, Koichi; Kurihara, Takeshi; Sato, Yasushi; Miyamoto, Yoshihiko; Kitamura, Shinji; Miyamoto, Hiroshi; Taguchi, Takahiro; Tsuneyama, Koichi; Takayama, Tetsuji
• 著者標目: Fujimoto, Shota; Muguruma, Naoki; Okamoto, Koichi; Kurihara, Takeshi; Sato, Yasushi; Miyamoto, Yoshihiko; Kitamura, Shinji; Miyamoto, Hiroshi; Taguchi, Takahiro; Tsuneyama, Koichi; Takayama, Tetsuji
• 出版事項: Ivyspring International Publisher
• 出版年月日等: 2018-03-21
• 出版年（W3CDTF）: 2018-03-21
• 並列タイトル等: c-KITを標的としたGastrointestinal stromal tumorsに対する近赤外蛍光イメージングとレーザー照射の新しいセラノスティクス
• タイトル（掲載誌）: Theranostics
• 授与機関名: 徳島大学
• 授与年月日: 2018-03-23
• 授与年月日（W3CDTF）: 2018-03-23
• 報告番号: 甲第3130号
• 学位: 博士（医学）
• 博論授与番号: 甲第3130号
• 本文の言語コード: eng
• 件名標目: gastrointestinal stromal tumors (GIST); c-KIT; fluorescence endoscopy; near-infrared photoimmunotherapy
• 対象利用者: 一般
• 一般注記: It is difficult to distinguish gastrointestinal stromal tumors (GISTs) from other types of submucosal tumors under conventional gastrointestinal endoscopy. We aimed to detect GISTs by molecular fluorescence imaging using a near-infrared (NIR) photosensitizer (IR700)-conjugated anti-c-KIT antibody and to treat GISTs by photoimmunotherapy with NIR irradiation as a non-invasive theranostic procedure. We also investigated the therapeutic mechanisms.Methods: Human GIST cell lines GIST-T1 and GIST-882M were incubated with IR700-conjugated anti-c-KIT antibody, IR700-12A8, and observed by confocal laser microscopy. Mice with GIST-T1 xenografts or rats with orthotopic xenografts were injected with IR700-12A8 or AF488-conjugated antibody, and observed under IVIS or autofluorescence imaging (AFI) endoscopy. GIST cells were treated with IR700-12A8 and NIR light in vitro and vivo, and cell viability, histology and apoptosis were evaluated.Results: Strong red fluorescence of IR700-12A8 was observed on the cell membrane of GIST cells and was gradually internalized into the cytoplasm. Tumor-specific accumulation of IR700-12A8 was observed in GIST-T1 xenografts in mice. Under AFI endoscopy, a strong fluorescence signal was observed in orthotopic GIST xenografts in rats through the normal mucosa covering the tumor. The percentage of dead cells significantly increased in a light-dose-dependent manner and both acute necrotic and late apoptotic cell death was observed with annexin/PI staining. Cleaved PARP expression was significantly increased after IR700-12A8-mediated NIR irradiation, which was almost completely reversed by NaN3. All xenograft tumors (7/7) immediately regressed and 4/7 tumors completely disappeared after IR700-12A8-mediated NIR irradiation. Histologic assessment and TUNEL staining revealed apoptosis in the tumors.Conclusion: NIR fluorescence imaging using IR700-12A8 and subsequent NIR irradiation could be a very effective theranostic technology for GIST, the underlying mechanism of which appears to involve acute necrosis and supposedly late apoptosis induced by singlet oxygen.
• DOI: info:doi/10.7150/thno.22027; https://doi.org/info:doi/10.7150/thno.22027
• 国立国会図書館永続的識別子: info:ndljp/pid/11092345; https://dl.ndl.go.jp/pid/11092345
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2018-05-04T12:13:37+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: https://repo.lib.tokushima-u.ac.jp/111436
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp