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首页> 外文期刊>British journal of neurosurgery >Fluorescence-guided resection of experimental malignant glioma using cetuximab-IRDye 800CW
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Fluorescence-guided resection of experimental malignant glioma using cetuximab-IRDye 800CW

机译：西妥昔单抗-IRDye 800CW荧光引导下切除实验性恶性神经胶质瘤

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The standard treatment for glioblastoma multiforme (GBM) remains maximal safe surgical resection. Here, we evaluated the ability of a systemically administered antibody-dye probe conjugate (cetuximab-IRDye 800CW) to provide sufficient fluorescent contrast for surgical resection of disease in both subcutaneous and orthotopic animal models of GBM. Multiple luciferase-positive GBM cell lines (D-54MG, U-87MG, and U-251MG; n = 5) were implanted in mouse flank and tumors were fluorescently imaged daily using a closed-field near-infrared (NIR) system after cetuximab-IRDye 800CW systemic administration. Orthotopic models were also generated (n = 5), and tumor resection was performed under white light and fluorescence guidance using an FDA-approved wide-field NIR imaging system. Residual tumor was monitored using luciferase imaging. Immunohistochemistry was performed to characterize tumor fluorescence, epidermal growth factor receptor (EGFR) expression, and vessel density. Daily imaging of tumors revealed an average tumor-to-background (TBR) of 4.5 for U-87MG, 4.1 for D-54MG, and 3.7 for U-251MG. Fluorescence intensity within the tumors peaked on day-1 after cetuximab-IRDye 800CW administration, however the TBR increased over time in two of the three cell lines. For the orthotopic model, TBR on surgery day ranged from 19 to 23 during wide-field, intraoperative imaging. Surgical resection under white light on day 3 after cetuximab-IRDye 800CW resulted in an average 41% reduction in luciferase signal while fluorescence-guided resection using wide-field NIR imaging resulted in a significantly (P = 0.001) greater reduction in luciferase signal (87%). Reduction of luciferase signal was found to correlate (R-0002"> 2 = 0.99) with reduction in fluorescence intensity. Fluorescence intensity was found to correlate (P < 0.05) with EGFR expression in D-54MG and U-251MG tumor types but not U-87MG. However, tumor fluorescence was found to correlate with vessel density for the U-87MG tumors. Here we show systemic administration of cetuximab-IRDye 800CW in combination with wide-field NIR imaging provided robust and specific fluorescence contrast for successful localization of disease in subcutaneous and orthotopic animal models of GBM.
机译：多形性胶质母细胞瘤（GBM）的标准治疗仍是最大程度的安全手术切除。在这里，我们评估了全身给药的抗体-染料探针偶联物（cetuximab-IRDye 800CW）为GBM皮下和原位动物模型中的手术切除提供足够的荧光对比的能力。西妥昔单抗治疗后，将多个荧光素酶阳性GBM细胞系（D-54MG，U-87MG和U-251MG; n = 5）植入小鼠后腹，并使用封闭场近红外（NIR）系统每天对肿瘤进行荧光成像-IRDye 800CW系统管理。还生成了原位模型（n = 5），并使用FDA批准的宽视野NIR成像系统在白光和荧光引导下进行了肿瘤切除。使用荧光素酶成像监测残余肿瘤。进行免疫组织化学以表征肿瘤荧光，表皮生长因子受体（EGFR）表达和血管密度。肿瘤的每日成像显示，U-87MG平均为4.5，D-54MG为4.1，U-251MG为3.7。给予西妥昔单抗-IRDye 800CW后第1天，肿瘤内的荧光强度达到峰值，但是三个细胞系中的两个中，TBR随时间增加。对于原位模型，在手术当天的大视野，术中成像期间，TBR的范围为19到23。西妥昔单抗-IRDye 800CW术后第3天在白光下进行手术切除可使萤光素酶信号平均降低41％，而使用广视野NIR成像的荧光引导切除术可使萤光素酶信号显着降低（P = 0.001）（87） ％）。在D-54MG和U-251MG肿瘤类型中，荧光素酶信号的减少与荧光强度的降低相关（R-0002“> 2 = 0.99），与D-54MG和U-251MG肿瘤类型的EGFR表达相关（P <0.05）。 U-87MG。然而，发现肿瘤荧光与U-87MG肿瘤的血管密度相关，在这里我们显示西妥昔单抗-IRDye 800CW的全身性给药与宽视野NIR成像相结合，为成功定位L-87MG提供了强大而特异性的荧光对比GBM的皮下和原位动物模型中发现这种疾病。

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