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New and effective EGFR-targeted fluorescence imaging technology for intraoperative rapid determination of lung cancer in freshly isolated tissue

文献类型：期刊论文

作者Li, Changjian2,5; Mi, Jiahui4; Wang, Yueqi3; Zhang, Zeyu2,5; Guo, Xiaoyong3,6; Zhou, Jian4; Hu, Zhenhua3; Tian, Jie1,2,3,5
刊名EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
出版日期2022-10-08
页码14
ISSN号1619-7070
关键词Intraoperative imaging technology Lung cancer Fluorescence-labeled antibody probe Epidermal growth factor receptor Surgical tumor resection
DOI10.1007/s00259-022-05975-7
通讯作者Zhou, Jian(zhoujian@bjmu.edu.cn) ; Hu, Zhenhua(zhenhua.hu@ia.ac.cn) ; Tian, Jie(jie.tian@ia.ac.cn)
英文摘要Purpose During lung cancer surgery, it is very important to define tumor boundaries and determine the surgical margin distance. In previous research, systemically application of fluorescent probes can help medical professionals determine the boundaries of tumors and find small tumors and metastases, thereby improving the accuracy of surgical resection. However, there are very few safe and effective probes that can be applied to clinical trials up to now, which limits the clinical application of fluorescence imaging. Here we developed a new technology that can quickly identify the tumor area in the resected lung tissue during the operation and distinguish the tumor boundary and metastatic lymph nodes. Experimental design For animal studies, a PDX model of lung cancer was established. The tumors, lungs, and peritumoral muscle tissues of tumor-bearing mice were surgically removed and incubated with a probe targeting epidermal growth factor receptor (EGFR) for 20 min, and then imaged by a closed-field near-infrared two-zone (NIR-II) fluorescence imaging system. For clinical samples, ten surgically removed lung tissues and 60 lymph nodes from 10 lung cancer patients undergoing radical resection were incubated with the targeting probe immediately after intraoperative resection and imaged to identify the tumor area and distinguish the tumor boundary and metastatic lymph nodes. The accuracy of fluorescence imaging was confirmed by HE staining and immunohistochemistry. Results The ex vivo animal imaging experiments showed a fluorescence enhancement of tumor tissue. For clinical samples, our results showed that this new technology yielded more than 85.7% sensitivity and 100% specificity in identifying the tumor area in the resected lung tissue. The average fluorescence tumor-to-background ratio was 2.5 +/- 1.3. Furthermore, we also used this technique to image metastatic lymph nodes intraoperatively and showed that metastatic lymph nodes have brighter fluorescence than normal lymph nodes, as the average fluorescence tumor-to-background signal ratio was 2.7 +/- 1.1. Calculations on the results of the fluorescence signal in relation to the number of metastatic lymph nodes yielded values of 77.8% for sensitivity and 92.1% for specificity. We expect this new technology to be a useful diagnostic tool for rapid intraoperative pathological detection and margin determination. Conclusions By using fluorescently labeled anti-human EGFR recombinant antibody scFv fragment to incubate freshly isolated tissues during surgery, the probes can quickly accumulate in lung cancer tissues, which can be used to quickly identify tumor areas in the resected lung tissues and distinguish tumor boundaries and find metastases in lymph nodes. This technology is expected to be used for rapid intraoperative pathological detection and margin determination.
WOS关键词SURGICAL NAVIGATION ; HEAD ; STATISTICS ; CETUXIMAB-IRDYE800CW ; SPECIFICITY ; SURGERY ; SAFETY ; MRI
资助项目National Natural Science Foundation of China[81227901] ; National Natural Science Foundation of China[81930053] ; National Natural Science Foundation of China[81827808] ; National Natural Science Foundation of China[81527805] ; National Natural Science Foundation of China[81971198] ; National Natural Science Foundation of China[81671851] ; National Natural Science Foundation of China[82003316] ; National Natural Science Foundation of China[92059203] ; National Natural Science Foundation of China[62027901] ; Fundamental Research Funds for the Central Universities[JKF-YG-22-B005] ; National Key Research and Development Program of China[2017YFA0205200] ; National Key Research and Development Program of China[2016YFC0103803] ; National Key Research and Development Program of China[2017YFA0700401] ; China Postdoctoral Science Foundation[2020M680301] ; China Postdoctoral Science Foundation[2019TQ0018] ; Chinese Academy of Sciences Youth Innovation Promotion Association[2018167] ; CAS Youth Interdisciplinary Team[JCTD-2021-08] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16021200] ; Chinese Academy of Sciences Key Technology Talent Program, Project of High-Level Talents Team Introduction in Zhuhai City (Zhuhai)[HLHPTP201703] ; Beijing Natural Science Foundation[7214266] ; Beijing Natural Science Foundation[JQ19027] ; Research and Development Fund of Peking University People's Hospital[RS2020-05]
WOS研究方向Radiology, Nuclear Medicine & Medical Imaging
语种英语
出版者SPRINGER
WOS记录号WOS:000864979300001
资助机构National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities ; National Key Research and Development Program of China ; China Postdoctoral Science Foundation ; Chinese Academy of Sciences Youth Innovation Promotion Association ; CAS Youth Interdisciplinary Team ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Chinese Academy of Sciences Key Technology Talent Program, Project of High-Level Talents Team Introduction in Zhuhai City (Zhuhai) ; Beijing Natural Science Foundation ; Research and Development Fund of Peking University People's Hospital
源URL[http://ir.ia.ac.cn/handle/173211/50349]  
专题自动化研究所_中国科学院分子影像重点实验室
通讯作者Zhou, Jian; Hu, Zhenhua; Tian, Jie
作者单位1.Jinan Univ, Zhuhai Peoples Hosp, Zhuhai Precis Med Ctr, Zhuhai 519000, Peoples R China
2.Beihang Univ, Sch Engn Med, Beijing 100191, Peoples R China
3.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing Key Lab Mol Imaging,State Key Lab Managem, Beijing, Peoples R China
4.Peking Univ, Dept Thorac Surg, Peoples Hosp, 11 Xi Zhi Men South Ave, Beijing 100190, Peoples R China
5.Beihang Univ, Minist Ind & Informat Technol, Key Lab Big Data Based Precis Med, Beijing 100191, Peoples R China
6.Chinese Peoples Liberat Army Gen Hosp, Med Ctr 3, Dept Gastroenterol, Beijing 100190, Peoples R China
推荐引用方式
GB/T 7714		 Li, Changjian,Mi, Jiahui,Wang, Yueqi,et al. New and effective EGFR-targeted fluorescence imaging technology for intraoperative rapid determination of lung cancer in freshly isolated tissue[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2022:14.
APA Li, Changjian.,Mi, Jiahui.,Wang, Yueqi.,Zhang, Zeyu.,Guo, Xiaoyong.,...&Tian, Jie.(2022).New and effective EGFR-targeted fluorescence imaging technology for intraoperative rapid determination of lung cancer in freshly isolated tissue.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,14.
MLA Li, Changjian,et al."New and effective EGFR-targeted fluorescence imaging technology for intraoperative rapid determination of lung cancer in freshly isolated tissue".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING (2022):14.

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来源：自动化研究所

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