Jingbo Wang1, Siyi Li2, Kun Wang3, Ling Zhu1, Lin Yang1, Yunjing Zhu1, Zhen Zhang2, Longwei Hu2, Yuan Yuan1, Qi Fan1, Jiliang Ren1, Gongxin Yang1, Weilong Ding1, Xiaoyu Zhou4, Junqi Cui5, Chunye Zhang5, Ying Yuan6, Ruimin Huang7, Jie Tian8, Xiaofeng Tao9. 1. Department of Radiology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China. 4. Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. 5. Department of Pathology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 6. Department of Radiology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. yuany83@163.com. 7. Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. rmhuang@simm.ac.cn. 8. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China. tian@ieee.org. 9. Department of Radiology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. cjr.taoxiaofeng@vip.163.com.
Abstract
INTRODUCTION: The postoperative survival of oral squamous cell carcinoma (SCC) relies on precise detection and complete resection of original tumors. The mucosal extension of the tumor is evaluated visually during surgery, but small and flat foci are difficult to detect. Real-time fluorescence imaging may improve detection of tumor margins. MATERIALS AND METHODS: In the current study, a peptide-based near-infrared (NIR) fluorescence dye, c-MET-binding peptide-indocyanine green (cMBP-ICG), which specifically targets tumor via c-MET binding, was synthetized. A prospective pilot clinical trial then was conducted with oral SCC patients and intraoperatively to assess the feasibility of cMBP-ICG used to detect tumors margins. Fluorescence was histologically correlated to determine sensitivity and specificity. RESULTS: The immunohistochemistry (IHC) results demonstrated increased c-Met expression in oral SCC compared with normal mucosa. Tumor-to-background ratios ranged from 2.71 ± 0.7 to 3.11 ± 1.2 in different concentration groups. From 10 patients with oral SCC, 60 specimens were collected from tumor margins. The sensitivity and specificity of discriminative value derived from cMBP-ICG application in humans were respectively 100% and 75%. CONCLUSIONS: Topical application of cMBP-ICG is feasible and safe for optimizing intraoperative visualization and tumor margin detection in oral SCC patients, which could clinically increase the probability of complete resections and improve oncologic outcomes.
INTRODUCTION: The postoperative survival of oral squamous cell carcinoma (SCC) relies on precise detection and complete resection of original tumors. The mucosal extension of the tumor is evaluated visually during surgery, but small and flat foci are difficult to detect. Real-time fluorescence imaging may improve detection of tumor margins. MATERIALS AND METHODS: In the current study, a peptide-based near-infrared (NIR) fluorescence dye, c-MET-binding peptide-indocyanine green (cMBP-ICG), which specifically targets tumor via c-MET binding, was synthetized. A prospective pilot clinical trial then was conducted with oral SCC patients and intraoperatively to assess the feasibility of cMBP-ICG used to detect tumors margins. Fluorescence was histologically correlated to determine sensitivity and specificity. RESULTS: The immunohistochemistry (IHC) results demonstrated increased c-Met expression in oral SCC compared with normal mucosa. Tumor-to-background ratios ranged from 2.71 ± 0.7 to 3.11 ± 1.2 in different concentration groups. From 10 patients with oral SCC, 60 specimens were collected from tumor margins. The sensitivity and specificity of discriminative value derived from cMBP-ICG application in humans were respectively 100% and 75%. CONCLUSIONS: Topical application of cMBP-ICG is feasible and safe for optimizing intraoperative visualization and tumor margin detection in oral SCC patients, which could clinically increase the probability of complete resections and improve oncologic outcomes.