徳島大学 教育・研究者情報データベース(EDB)

1. (英) Fujimoto Shota / (日) 藤本 将太 / (読) ふじもと しょうた

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2. 六車 直樹

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3. 岡本 耕一([徳島大学.病院.診療科.内科.消化器内科])

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4. (英) Kurihara Takeshi

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5. 佐藤 康史([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域消化器・総合内科学])

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6. (英) Miyamoto Yoshihiko / (日) 宮本 佳彦 / (読) みやもと よしひこ

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7. 北村 晋志

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8. 宮本 弘志([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学]/[徳島大学.病院.診療科.内科.消化器内科])

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9. (英) Taguchi Takahiro

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10. 常山 幸一([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.疾患病理学])

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11. 高山 哲治([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])

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

(英) 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. 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 and vivo, and cell viability, histology and apoptosis were evaluated. 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 NaN. 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. 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.

1. (英) Article.ELocationID: 10.7150/thno.22027

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) KeywordList.Keyword: c-KIT

4. (英) KeywordList.Keyword: fluorescence endoscopy

5. (英) KeywordList.Keyword: gastrointestinal stromal tumors (GIST)

6. (英) KeywordList.Keyword: near-infrared photoimmunotherapy

7. (英) CoiStatement: Competing Interests: The authors have declared that no competing interest exists.