Transferrin receptor 1 targeted optical imaging for identifying glioma margin in mouse models
Transferrin receptor 1 targeted optical imaging for identifying glioma margin in mouse models
复制标题
转铁蛋白受体 1 靶向光学成像用于识别小鼠模型中的神经胶质瘤边缘
DOI：
10.1007/s11060-020-03527-3
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发表时间：
2020-05-13
影响因子：
3.9
通讯作者：
Chen, Zhong-Ping
中科院分区：
文献类型：
--
作者：
Ni, Xiang-Rong;Zhao, Yi-Ying;Chen, Zhong-Ping
目的利用光学分子影像技术对颅内胶质母细胞瘤（GBM）进行无差别检测，帮助神经外科医生有效切除肿瘤。转铁蛋白受体1（Transferrin receptor 1，TfR 1）是GBM诊断和治疗的靶点. TfR 1靶向肽CRTIGPSVC（CRT）显示穿过血脑屏障（BBB）并在GBM组织中以高水平积累。在这项研究中，我们合成了一个TfR 1靶向的近红外荧光（NIRF）探针，Cy 5-CRT，用于识别GBM组织边缘的小鼠模型。方法在皮下和原位GBM小鼠模型中初步证实了TfR 1在GBM中的过表达和Cy 5-CRT的肿瘤特异性归巢能力。然后，我们研究了Cy 5-CRT用于识别原位GBM异种移植物中的肿瘤边缘的可行性。最后，我们比较了Cy 5-CRT和临床上使用的荧光素钠在识别肿瘤边缘方面的作用。结果Cy 5-CRT在GBM组织中特异性积聚，并在原位GBM小鼠中以异常对比度检测肿瘤负荷，使得能够在NIRF实时成像条件下进行荧光引导的GBM切除。重要的是，Cy 5-CRT比荧光素钠更清楚地识别GBM组织边缘。结论TfR 1靶向光学探针Cy 5-CRT可特异性区分肿瘤组织和周围正常脑组织，具有较高的灵敏度，有望用于精确手术切除GBM。
Objective Optical molecular imaging technology that indiscriminately detects intracranial glioblastoma (GBM) can help neurosurgeons effectively remove tumor masses. Transferrin receptor 1 (TfR 1) is a diagnostic and therapeutic target in GBM. A TfR 1-targeted peptide, CRTIGPSVC (CRT), was shown to cross the blood brain barrier (BBB) and accumulate at high levels in GBM tissues. In this study, we synthesized a TfR 1-targeted near-infrared fluorescent (NIRF) probe, Cy5-CRT, for identifying the GBM tissue margin in mouse models. Methods We initially confirmed the overexpression of TfR 1 in GBM and the tumor-specific homing ability of Cy5-CRT in subcutaneous and orthotopic GBM mouse models. We then examined the feasibility of Cy5-CRT for identifying the tumor margin in orthotopic GBM xenografts. Finally, we compared Cy5-CRT with the clinically used fluorescein sodium in identifying tumor margins. Results Cy5-CRT specifically accumulated in GBM tissues and detected the tumor burden with exceptional contrast in mice with orthotopic GBM, enabling fluorescence-guided GBM resection under NIRF live imaging conditions. Importantly, Cy5-CRT recognized the GBM tissue margin more clearly than fluorescein sodium. Conclusions The TfR 1-targeted optical probe Cy5-CRT specifically differentiates tumor tissues from the surrounding normal brain with high sensitivity, indicating its potential application for the precise surgical removal of GBM.