NIR-II fluorescence imaging-guided colorectal cancer surgery targeting CEACAM5 by a nanobodyResearch in context
Xiaoyong Guo,
Changjian Li,
Xiaohua Jia,
Yawei Qu,
Miaomiao Li,
Caiguang Cao,
Zeyu zhang,
Qiaojun Qu,
Shuangling Luo,
Jianqiang Tang,
Haifeng Liu,
Zhenhua Hu,
Jie Tian
Affiliations
Xiaoyong Guo
Clinical College of Armed Police General Hospital of Anhui Medical University, Department of Gastroenterology of The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
Changjian Li
School of Engineering Medicine, Beihang University, Beijing, 100191, China; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, 100191, China
Xiaohua Jia
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
Yawei Qu
Department of Control Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, China; Beijing Mentougou District Hospital, Beijing, 102300, China
Miaomiao Li
Clinical College of Armed Police General Hospital of Anhui Medical University, Department of Gastroenterology of The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
Caiguang Cao
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China
Zeyu zhang
School of Engineering Medicine, Beihang University, Beijing, 100191, China; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, 100191, China
Qiaojun Qu
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; College of Medical Imaging, Shanxi Medical University, Taiyuan, 030001, China
Shuangling Luo
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, China
Jianqiang Tang
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Corresponding author. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Haifeng Liu
Clinical College of Armed Police General Hospital of Anhui Medical University, Department of Gastroenterology of The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; Beijing Mentougou District Hospital, Beijing, 102300, China; Corresponding author. Clinical College of Armed Police General Hospital of Anhui Medical University, Department of Gastroenterology of The Third Medical Center of Chinese PLA General Hospital, No. 69 Yongding Road, Hai Dian District, Beijing, 100039, China.
Zhenhua Hu
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding author. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing, 100190, China.
Jie Tian
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Medicine, Beihang University, Beijing, 100191, China; Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, 100191, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding author. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing, 100190, China.
Summary: Background: Surgery is the cornerstone of colorectal cancer (CRC) treatment, yet complete removal of the tumour remains a challenge. The second near-infrared window (NIR-II, 1000–1700 nm) fluorescent molecular imaging is a novel technique, which has broad application prospects in tumour surgical navigation. We aimed to evaluate the ability of CEACAM5-targeted probe for CRC recognition and the value of NIR-II imaging-guided CRC resection. Methods: We constructed the probe 2D5-IRDye800CW by conjugated anti-CEACAM5 nanobody (2D5) with near-infrared fluorescent dye IRDye800CW. The performance and benefits of 2D5-IRDye800CW at NIR-II were confirmed by imaging experiments in mouse vascular and capillary phantom. Then mouse colorectal cancer subcutaneous tumour model (n = 15), orthotopic model (n = 15), and peritoneal metastasis model (n = 10) were constructed to investigate biodistribution of probe and imaging differences between NIR-I and NIR-II in vivo, and then tumour resection was guided by NIR-II fluorescence. Fresh human colorectal cancer specimens were incubated with 2D5-IRDye800CW to verify its specific targeting ability. Findings: 2D5-IRDye800CW had an NIR-II fluorescence signal extending to 1600 nm and bound specifically to CEACAM5 with an affinity of 2.29 nM. In vivo imaging, 2D5-IRDye800CW accumulated rapidly in tumour (15 min) and could specifically identify orthotopic colorectal cancer and peritoneal metastases. All tumours were resected under NIR-II fluorescence guidance, even smaller than 2 mm tumours were detected, and NIR-II had a higher tumour-to-background ratio than NIR-I (2.55 ± 0.38, 1.94 ± 0.20, respectively). 2D5-IRDye800CW could precisely identify CEACAM5-positive human colorectal cancer tissue. Interpretation: 2D5-IRDye800CW combined with NIR-II fluorescence has translational potential as an aid to improve R0 surgery of colorectal cancer. Fundings: This study was supported by Beijing Natural Science Foundation (JQ19027), the National Key Research and Development Program of China (2017YFA0205200), National Natural Science Foundation of China (NSFC) (61971442, 62027901, 81930053, 92059207, 81227901, 82102236), Beijing Natural Science Foundation (L222054), CAS Youth Interdisciplinary Team (JCTD-2021-08), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16021200), the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703), the Fundamental Research Funds for the Central Universities (JKF-YG-22-B005) and Capital Clinical Characteristic Application Research (Z181100001718178). The authors would like to acknowledge the instrumental and technical support of the multi-modal biomedical imaging experimental platform, Institute of Automation, Chinese Academy of Sciences.
