一种转铁蛋白靶向磁性/荧光双模探针显著提高了非小细胞肺癌的诊断水平。
A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer.
作者信息
Cai Jiali, Gu Bingxin, Cao Fengwen, Liu Shiyuan
机构信息
Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.
出版信息
Oncotarget. 2016 Jun 28;7(26):40047-40059. doi: 10.18632/oncotarget.9482.
To enhance the diagnosis of non-small cell lung cancer (NSCLC), we prepared a dual-modal probe Cy5.5-Tf-Gd-DTPA. Gd-DTPA and near-infrared (NIR) dyes were conjugated to holo-Transferrin (Tf) sequentially, the result of ICP-AES and UV showed 25 Gd ions and 1 Cy5.5 could be loaded per protein, respectively. The calculated longitudinal relaxivity R1 of Cy5.5-Tf-DTPA-Gd was 4.21 mM-1S-1 per Gd while that of Magnevist (Gd-DTPA) was only 4.02 mM-1S-1. Confocal laser scanning microscopy and immunohistochemical analyses revealed that the Cy5.5-Tf-DTPA-Gd was localized and accumulated in cytoplasmic vesicles; the cell toxicity assay showed no apparent toxicity. MR and NIR imaging of mice with subcutaneous H1299 xenografte tumors following intravenous injection of Cy5.5-Tf-DTPA-Gd revealed a strong positive contrast of the tumors, which caused a longer lasting enhancement of the MRI signal and fluorescence signal. Taken together, these studies indicate that Cy5.5-Tf-DTPA-Gd could be a good agent for MR/NIRF dual mode applications to detect both tumor in situ and its metastasis.
为提高非小细胞肺癌（NSCLC）的诊断水平，我们制备了一种双模态探针Cy5.5-Tf-Gd-DTPA。钆喷酸葡胺（Gd-DTPA）和近红外（NIR）染料依次与全转铁蛋白（Tf）偶联，电感耦合等离子体发射光谱（ICP-AES）和紫外（UV）检测结果表明，每个蛋白质分子可分别负载25个钆离子和1个Cy5.5。计算得出，Cy5.5-Tf-DTPA-Gd中每个钆离子的纵向弛豫率R1为4.21 mM-1S-1，而马根维显（Gd-DTPA）仅为4.02 mM-1S-1。共聚焦激光扫描显微镜和免疫组织化学分析显示，Cy5.5-Tf-DTPA-Gd定位于细胞质囊泡并在其中积聚；细胞毒性试验表明无明显毒性。静脉注射Cy5.5-Tf-DTPA-Gd后，对皮下接种H1299异种移植瘤的小鼠进行磁共振成像（MR）和近红外成像（NIR），结果显示肿瘤有强烈的阳性对比，导致MRI信号和荧光信号增强持续时间更长。综上所述，这些研究表明Cy5.5-Tf-DTPA-Gd可能是一种用于MR/NIRF双模态应用以检测原位肿瘤及其转移的良好试剂。
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