First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800
First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800
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DOI：
10.1007/s11060-018-2854-0
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发表时间：
2018-08-01
影响因子：
3.9
通讯作者：
Rosenthal, Eben L.
中科院分区：
文献类型：
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作者：
Miller, Sarah E.;Tummers, Willemieke S.;Rosenthal, Eben L.
最大程度的手术切除，最低的发病率仍然是胶质母细胞瘤患者生存的关键，我们假设，它可以改善术中肿瘤检测的增强。在一项临床研究中，我们确定了治疗性抗体是否可以在切除术中用于术中成像。术中和离体进行肿瘤和组织学阴性肿瘤周围组织的近红外荧光成像。荧光测量为平均荧光强度（MFI），通过比较肿瘤和组织学上未受累组织的MFI来计算肿瘤与背景比（TBRs）。术前成像上对比增强（CE）肿瘤组织的平均TBR（4.0 ± 0.5）显著高于非CE肿瘤（1.2 ± 0.3; p = 0.02）。100 mg剂量组的TBR高于50 mg剂量组（4.3 vs. 3.6）。在闭野环境中，最小可检测肿瘤体积为70 mg（50 mg染料）和10 mg（100 mg染料）。在石蜡包埋组织切片上，荧光与肿瘤的组织学证据呈正相关。计算了肿瘤荧光检测活肿瘤的灵敏度和特异性，发现荧光是高度灵敏的（50 mg剂量为73.0%，100 mg剂量为98.2%）和特异性（50 mg剂量为66.3%，69.8%，对于100 mg剂量），而正常的肿瘤周围组织显示最小的荧光。人体研究证实了基于抗体的CE胶质母细胞瘤成像的可行性和安全性。
Maximizing extent of surgical resection with the least morbidity remains critical for survival in glioblastoma patients, and we hypothesize that it can be improved by enhancements in intraoperative tumor detection. In a clinical study, we determined if therapeutic antibodies could be repurposed for intraoperative imaging during resection.Fluorescently labeled cetuximab-IRDye800 was systemically administered to three patients 2 days prior to surgery. Near-infrared fluorescence imaging of tumor and histologically negative peri-tumoral tissue was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratios (TBRs) were calculated by comparing MFIs of tumor and histologically uninvolved tissue.The mean TBR was significantly higher in tumor tissue of contrast-enhancing (CE) tumors on preoperative imaging (4.0 +/- 0.5) compared to non-CE tumors (1.2 +/- 0.3; p = 0.02). The TBR was higher at a 100 mg dose than at 50 mg (4.3 vs. 3.6). The smallest detectable tumor volume in a closed-field setting was 70 mg with 50 mg of dye and 10 mg with 100 mg. On sections of paraffin embedded tissues, fluorescence positively correlated with histological evidence of tumor. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (73.0% for 50 mg dose, 98.2% for 100 mg dose) and specific (66.3% for 50 mg dose, 69.8% for 100 mg dose) for viable tumor tissue in CE tumors while normal peri-tumoral tissue showed minimal fluorescence.This first-in-human study demonstrates the feasibility and safety of antibody based imaging for CE glioblastomas.