Increased precision of orthotopic and metastatic breast cancer surgery guided by matrix metalloproteinase-activatable near-infrared fluorescence probes.
Increased precision of orthotopic and metastatic breast cancer surgery guided by matrix metalloproteinase-activatable near-infrared fluorescence probes.
复制标题
使用靶向近红外荧光探针进行成像引导手术术中识别肝癌微病灶
DOI：
10.1038/srep14197
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发表时间：
2015-09-23
影响因子：
4.6
通讯作者：
Tian J
中科院分区：
文献类型：
--
作者：
Chi C;Zhang Q;Mao Y;Kou D;Qiu J;Ye J;Wang J;Wang Z;Du Y;Tian J
先进的医学成像技术允许使用荧光分子成像引导的乳腺癌手术（FMI引导的BCS）来特异性标记肿瘤细胞，并在手术中精确区分肿瘤边缘和正常组织，这是医学领域的一个主要挑战。在这里，我们开发了一个手术导航系统，用于实时FMI引导BCS。在裸鼠中建立了来源于高转移性4 T1-luc乳腺癌细胞的肿瘤，该细胞表现出基质金属蛋白酶（MMP）和人表皮生长因子受体2（HER 2）的高表达;这些小鼠注射了智能MMP靶向和“始终在线”HER 2靶向近红外（NIR）荧光探针。将荧光信号成像以评估探针与肿瘤和转移位点的体内结合。然后，原位和转移性乳腺肿瘤在我们的系统的指导下被精确地切除。实验结果表明，新方法可使小鼠术后存活率提高50%。苏木素和伊红染色以及MMP 2和CD 11b的免疫组化染色进一步证实了肿瘤解剖的精确性。我们的方法促进了乳腺癌肿瘤的准确检测和完全切除，并提供了一种在手术过程中定义乳腺癌分子分类的方法，从而提高了手术成功率和生存率。
Advanced medical imaging technology has allowed the use of fluorescence molecular imaging-guided breast cancer surgery (FMI-guided BCS) to specifically label tumour cells and to precisely distinguish tumour margins from normal tissues intra-operatively, a major challenge in the medical field. Here, we developed a surgical navigation system for real-time FMI-guided BCS. Tumours derived from highly metastatic 4T1-luc breast cancer cells, which exhibit high expression of matrix metalloproteinase (MMP) and human epidermal growth factor receptor 2 (HER2), were established in nude mice; these mice were injected with smart MMP-targeting and “always-on” HER2-targeting near-infrared (NIR) fluorescent probes. The fluorescence signal was imaged to assess in vivo binding of the probes to the tumour and metastatic sites. Then, orthotopic and metastatic breast tumours were precisely removed under the guidance of our system. The post-operative survival rate of mice was improved by 50% with the new method. Hematoxylin and eosin staining and immunohistochemical staining for MMP2 and CD11b further confirmed the precision of tumour dissection. Our method facilitated the accurate detection and complete removal of breast cancer tumours and provided a method for defining the molecular classification of breast cancer during surgery, thereby improving prognoses and survival rates.