International Journal of Nanomedicine (Nov 2017)
Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model
Abstract
Yang Du,1,2,* Ting Sun,3,* Xiaolong Liang,4,* Yuan Li,3 Zhengyu Jin,3 Huadan Xue,3 Yihong Wan,5 Jie Tian1,2 1CAS Key Laboratory of Molecular Imaging, 2The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, 3Department of Radiology, Peking Union Medical College Hospital, 4Department of Ultrasound, Peking University Third Hospital, Beijing, China; 5Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA *These authors contributed equally to this work Abstract: 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. Keywords: PD-1, programmed cell death-1, near-infrared fluorescence (NIRF), breast cancer, image-guided surgery, immunotherapy, fluorescence imaging
