ID | 111436 |
タイトル別表記 | 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
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著者 |
藤本, 将太
徳島大学大学院医科学教育部(医学専攻)
Kurihara, Takeshi
Tokushima University
Miyamoto, Yoshihiko
Tokushima University
Taguchi, Takahiro
Tokushima University
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キーワード | gastrointestinal stromal tumors (GIST)
c-KIT
fluorescence endoscopy
near-infrared photoimmunotherapy
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資料タイプ |
学位論文
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抄録 | 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. |
掲載誌名 |
Theranostics
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ISSN | 18387640
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出版者 | Ivyspring International Publisher
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巻 | 8
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号 | 9
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開始ページ | 2313
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終了ページ | 2328
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発行日 | 2018-03-21
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Shota Fujimotoの学位論文として提出され,学位審査・授与の対象となっている。 |
権利情報 | © 2018 Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3130号
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学位記番号 | 甲医第1364号
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学位授与年月日 | 2018-03-23
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
医学系
病院
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