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

doi:10.1007/s00259-022-05975-7

	New and effective EGFR-targeted fluorescence imaging technology for intraoperative rapid determination of lung cancer in freshly isolated tissue
	Li, Changjian 1,2; Mi, Jiahui 3; Wang, Yueqi4 ; Zhang, Zeyu1,2 ; Guo, Xiaoyong 4,5; Zhou, Jian 3; Hu, Zhenhua4 ; Tian, Jie 1,2,4,6
发表期刊	EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN	1619-7070
	2022-10-08
页码	14
通讯作者	Zhou, Jian(zhoujian@bjmu.edu.cn) ; Hu, Zhenhua(zhenhua.hu@ia.ac.cn) ; Tian, Jie(jie.tian@ia.ac.cn)
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.
关键词	Intraoperative imaging technology Lung cancer Fluorescence-labeled antibody probe Epidermal growth factor receptor Surgical tumor resection
DOI	10.1007/s00259-022-05975-7
关键词[WOS]	SURGICAL NAVIGATION ; HEAD ; STATISTICS ; CETUXIMAB-IRDYE800CW ; SPECIFICITY ; SURGERY ; SAFETY ; MRI
收录类别	SCI
语种	英语
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]
项目资助者	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
WOS研究方向	Radiology, Nuclear Medicine & Medical Imaging
WOS类目	Radiology, Nuclear Medicine & Medical Imaging
WOS记录号	WOS:000864979300001
出版者	SPRINGER
引用统计	被引频次：12[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/50350
专题	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.Beihang Univ, Sch Engn Med, Beijing 100191, Peoples R China 2.Beihang Univ, Minist Ind & Informat Technol, Key Lab Big Data Based Precis Med, Beijing 100191, Peoples R China 3.Peking Univ, Dept Thorac Surg, Peoples Hosp, 11 Xi Zhi Men South Ave, Beijing 100190, Peoples R China 4.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing Key Lab Mol Imaging,State Key Lab Managem, Beijing, Peoples R China 5.Chinese Peoples Liberat Army Gen Hosp, Med Ctr 3, Dept Gastroenterol, Beijing 100190, Peoples R China 6.Jinan Univ, Zhuhai Peoples Hosp, Zhuhai Precis Med Ctr, Zhuhai 519000, Peoples R China
通讯作者单位	中国科学院自动化研究所
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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