NIR-II fluorescence imaging-guided colorectal cancer surgery targeting CEACAM5 by a nanobody
Xiaoyong Guo1, Changjian Li2, Xiaohua Jia3
1Clinical 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.
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.
Insights
A novel probe targeting CEACAM5, combined with second near-infrared window (NIR-II) fluorescence imaging, shows promise for improving colorectal cancer (CRC) surgery by enabling precise detection and resection of tumors.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Surgical Navigation
Background:
- Colorectal cancer (CRC) surgery requires complete tumor removal, which can be challenging.
- Second near-infrared window (NIR-II) fluorescent molecular imaging offers potential for enhanced tumor surgical navigation.
Purpose of the Study:
- To evaluate a CEACAM5-targeted probe for colorectal cancer recognition.
- To assess the value of NIR-II imaging-guided colorectal cancer resection.
Main Methods:
- Developed a probe (2D5-IRDye800CW) by conjugating an anti-CEACAM5 nanobody with a near-infrared dye.
- Validated probe performance in phantom models and established colorectal cancer models in mice (subcutaneous, orthotopic, peritoneal metastasis).
- Investigated probe biodistribution, compared NIR-I and NIR-II imaging, and guided tumor resection using NIR-II fluorescence. Verified targeting in human colorectal cancer specimens.
Main Results:
- The 2D5-IRDye800CW probe exhibited NIR-II fluorescence and specific binding to CEACAM5.
- In vivo imaging demonstrated rapid tumor accumulation and specific identification of orthotopic and metastatic colorectal cancer.
- NIR-II fluorescence guidance enabled detection and resection of tumors as small as 2 mm, with a higher tumor-to-background ratio than NIR-I.
Conclusions:
- The 2D5-IRDye800CW probe combined with NIR-II fluorescence imaging has translational potential.
- This approach can aid in improving R0 resection rates for colorectal cancer surgery.
More Related Videos
15:17Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
12:24Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012