Du Yang, Sun Ting, Liang Xiaolong, Li Yuan, Jin Zhengyu, Xue Huadan, Wan Yihong, Tian Jie
CAS Key Laboratory of Molecular Imaging.
The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences.
Int J Nanomedicine. 2017 Nov 21;12:8337-8351. doi: 10.2147/IJN.S149235. eCollection 2017.
An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model. Fluorescence molecular imaging was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging was performed to monitor tumor growth and evaluate postsurgical tumor residuals, recurrences, and metastases. The PD-1-IRDye800CW exhibited a specific signal at the tumor region compared with the IgG control. Furthermore, PD-1-IRDye800CW-guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases and thus improved survival rate. Our study demonstrates the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from tumor residuals.
一种准确识别微小肿瘤残留的术中技术可降低手术切缘阳性的风险。多条证据支持PD -1在乳腺癌中的表达及免疫治疗效果。在此，我们试图开发一种用于体内乳腺肿瘤成像和图像引导手术的荧光标记PD -1探针。还评估了PD -1单克隆抗体（PD -1 mAb）作为术后辅助免疫治疗的疗效。在具有免疫活性的4T1小鼠肿瘤模型中开发并检测了PD -1 -IRDye800CW在肿瘤成像和图像引导肿瘤切除中的应用。进行荧光分子成像以监测探针的生物分布和术中成像。进行生物发光成像以监测肿瘤生长并评估术后肿瘤残留、复发和转移。与IgG对照相比，PD -1 -IRDye800CW在肿瘤区域表现出特异性信号。此外，PD -1 -IRDye800CW引导的手术联合PD -1辅助免疫治疗可抑制肿瘤再生长和微肿瘤转移，从而提高生存率。我们的研究证明了使用PD -1 -IRDye800CW进行乳腺肿瘤成像和图像引导肿瘤切除的可行性。此外，PD -1 mAb辅助免疫治疗可减少肿瘤残留引起的癌症复发和转移。
