Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China.
Nanoscale. 2017 Jun 14;9(23):7930-7940. doi: 10.1039/c7nr01077j.
Surgery is a mainstay to treat malignant brain tumors. However, due to the infiltrative nature of these tumors, it is a great challenge for surgeons to accurately identify and excise all the tumor foci. EGFRvIII, a variant of epidermal growth factor receptor (EGFR), is found in 20% of glioblastoma cases, which is the brain tumor with the highest malignancy. In this study, we developed an EGFRvIII-targeted nanoprobe to guide glioblastoma surgery by pre-operatively defining the tumor boundary via magnetic resonance imaging (MRI) and intra-operatively guiding resection by surface-enhanced resonance Raman scattering (SERRS) imaging. In vivo MRI studies show that this nanoprobe delineates an orthotopic EGFRvIII+ U87MG glioblastoma xenograft with a higher target to background ratio than the control nanoprobe without targeting specificity. With the assistance of a handheld Raman scanner, this nanoprobe successfully guided EGFRvIII+ glioblastoma resection by tracking its characteristic SERRS signal peaks. Ex vivo Raman microscopy and histological images verified that this nanoprobe precisely demarcated the glioblastoma boundary and no residual neoplastic foci were observed in the tumor bed. This dual-modal nanoprobe not only precisely guided glioblastoma resection, but also overcame the brain shift induced false-positive signal by real-timely co-registering pre-operative and intra-operative images. This nanoprobe is promising for the improvement in diagnostic accuracy and surgical outcome of EGFRvIII+ glioblastoma.
手术是治疗恶性脑肿瘤的主要手段。然而，由于这些肿瘤具有浸润性，对于外科医生来说，准确识别和切除所有肿瘤病灶是一个巨大的挑战。表皮生长因子受体（EGFR）的变体 EGFRvIII 存在于 20%的胶质母细胞瘤病例中，是恶性程度最高的脑肿瘤。在这项研究中，我们开发了一种针对 EGFRvIII 的纳米探针，通过磁共振成像（MRI）术前定义肿瘤边界，并通过表面增强共振拉曼散射（SERRS）成像术中引导切除，来指导胶质母细胞瘤手术。体内 MRI 研究表明，与没有靶向特异性的对照探针相比，该纳米探针可描绘出具有更高靶背比的原位 EGFRvIII+U87MG 胶质母细胞瘤异种移植物。在手持式拉曼扫描仪的协助下，该纳米探针通过跟踪其特征性 SERRS 信号峰，成功地引导了 EGFRvIII+胶质母细胞瘤的切除。离体拉曼显微镜和组织学图像证实，该纳米探针精确地标定了胶质母细胞瘤的边界，在肿瘤床中未观察到残留的肿瘤病灶。这种双模纳米探针不仅精确地指导了胶质母细胞瘤的切除，而且通过实时配准术前和术中图像克服了脑移位引起的假阳性信号。该纳米探针有望提高 EGFRvIII+胶质母细胞瘤的诊断准确性和手术结果。
