In Vivo Fluorescence Imaging of Gastrointestinal Stromal Tumors Using Fluorophore-Conjugated Anti-KIT Antibody
In Vivo Fluorescence Imaging of Gastrointestinal Stromal Tumors Using Fluorophore-Conjugated Anti-KIT Antibody
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DOI：
10.1245/s10434-013-3172-6
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发表时间：
2013-12-01
影响因子：
3.7
通讯作者：
Sicklick, Jason K.
中科院分区：
文献类型：
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作者：
Metildi, Cristina A.;Tang, Chih-Min;Sicklick, Jason K.
背景胃肠道间质瘤（GIST）通常以KIT过表达为特征。无肿瘤边缘和疾病的完全细胞减少是治疗的主要支柱。我们假设荧光标记的抗KIT抗体可以在体内标记GIST。本研究中使用自发发生盲肠GIST的KIT K641 E（+/-）转基因小鼠，C57 BL/6小鼠作为对照。在荧光成像前24小时，通过尾静脉递送Alexa 488荧光团缀合的抗KIT抗体。荧光腹腔镜检查后，处死小鼠。对胃肠道进行大体检查，检查肿瘤，然后进行荧光成像。收集肿瘤进行组织学确认。KIT K641 E（+/-）小鼠和C57 BL/6对照小鼠接受抗KIT抗体或同位素对照抗体。荧光腹腔镜具有较高的肿瘤信号背景噪声比。在对活体荧光和亮光图像进行盲态审查后，有2个假阳性和0个假阴性结果。准确率为92%。联合诊断的敏感性、特异性、阳性预测值和阴性预测值分别为100、87、85和100%。在这项研究中，我们提出了一种在体内荧光标记的GIST在小鼠模型的方法。几个可翻译的应用包括：腹腔镜分期;腹膜转移的可视化;边缘状态的评估;内镜下GIST与其他良性粘膜下肿瘤的鉴别;以及疾病反应的纵向监测。这种新方法具有明确的临床应用，值得进一步研究和开发。
Background. Gastrointestinal stromal tumors (GISTs) are frequently characterized by KIT overexpression. Tumor-free margins and complete cytoreduction of disease are mainstays of treatment. We hypothesized that fluorescently labeled anti-KIT antibodies can label GIST in vivo.Methods. KIT K641E(+/-) transgenic mice that spontaneously develop cecal GISTs were used in this study, with C57BL/6 mice serving as controls. Alexa 488 fluorophore-conjugated anti-KIT antibodies were delivered via the tail vein 24 h prior to fluorescence imaging. Following fluorescence laparoscopy, mice were sacrificed. The gastrointestinal tracts were grossly examined for tumors followed by fluorescence imaging. Tumors were harvested for histologic confirmation.Results. KIT K641E(+/-) mice and C57BL/6 control mice received anti-KIT antibody or isotope control antibody. Fluorescence laparoscopy had a high tumor signal-to-background noise ratio. Upon blinded review of intravital fluorescence and bright light images, there were 2 false-positive and 0 false-negative results. The accuracy was 92 %. The sensitivity, specificity, positive and negative predictive values were 100, 87, 85, and 100 %, respectively, for the combined modalities.Conclusions. In this study, we present a method for in vivo fluorescence labeling of GIST in a murine model. Several translatable applications include: laparoscopic staging; visualization of peritoneal metastases; assessment of margin status; endoscopic differentiation of GISTs from other benign submucosal tumors; and longitudinal surveillance of disease response. This novel approach has clear clinical applications that warrant further research and development.