A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors.
A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors.
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DOI：
10.7150/thno.22027
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发表时间：
2018
期刊：
影响因子：
12.4
通讯作者：
Takayama T
中科院分区：
文献类型：
--
作者：
Fujimoto S;Muguruma N;Okamoto K;Kurihara T;Sato Y;Miyamoto Y;Kitamura S;Miyamoto H;Taguchi T;Tsuneyama K;Takayama T
胃肠道间质瘤（gist）与其他类型的粘膜下肿瘤在常规胃肠道内镜下难以区分。我们的目的是通过使用近红外（NIR）光敏剂（IR700）偶联抗c- kit抗体的分子荧光成像检测gist，并通过NIR照射的光免疫疗法作为非侵入性治疗方法治疗gist。我们还研究了治疗机制。方法：用ir700偶联抗c- kit抗体IR700-12A8培养人GIST细胞株GIST- t1和GIST- 882m，激光共聚焦显微镜观察。用IR700-12A8或af488偶联抗体注射GIST-T1异种移植物小鼠或原位异种移植物大鼠，在IVIS或AFI内镜下观察。体外和体内分别用IR700-12A8和近红外光处理GIST细胞，观察细胞活力、组织学和凋亡情况。结果：IR700-12A8在GIST细胞的细胞膜上观察到强烈的红色荧光，并逐渐内化到细胞质中。在小鼠GIST-T1异种移植物中观察到IR700-12A8的肿瘤特异性积累。在AFI内镜下，通过覆盖肿瘤的正常黏膜，观察到大鼠原位GIST异种移植物有强烈的荧光信号。膜联蛋白/PI染色可观察到急性坏死和晚期凋亡细胞的死亡。在ir700 - 12a8介导的近红外照射后，Cleaved PARP的表达显著增加，而NaN3几乎完全逆转了这一趋势。在ir700 - 12a8介导的近红外照射后，所有异种移植肿瘤（7/7）立即消退，4/7肿瘤完全消失。组织学及TUNEL染色显示肿瘤细胞凋亡。结论：IR700-12A8近红外荧光成像及后续近红外照射是一种非常有效的GIST治疗技术，其潜在机制可能与单线态氧诱导的急性坏死和可能的晚期凋亡有关。
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.
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DOI：
10.2217/fon.09.109
发表时间：
2009-11
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Kosaka N;Ogawa M;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
12.4
作者：
Jing H;Weidensteiner C;Reichardt W;Gaedicke S;Zhu X;Grosu AL;Kobayashi H;Niedermann G
通讯作者：
Niedermann G
影响因子：
24.5
作者：
Mitsunaga M;Kosaka N;Choyke PL;Young MR;Dextras CR;Saud SM;Colburn NH;Sakabe M;Nagano T;Asanuma D;Urano Y;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
6.3
作者：
Izumi, Dasiuke;Yoshida, Naoya;Baba, Hideo
通讯作者：
Baba, Hideo
影响因子：
3.5
作者：
Lin, Huiyun;Zhang, Rongxiao;Pogue, Brian W.
通讯作者：
Pogue, Brian W.