Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy

doi:10.1007/s00259-022-05922-6

	Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy
	Huang, Wenhui 1,2,3; Wang, Kun2 ; Huang, Weiyuan 4; He, Zicong 3; Zhang, Jingming 5; Zhang, Bin 3; Xiong, Zhiyuan 6; Gillen, Kelly McCabe 7; Li, Wenzhe 8; Chen, Feng 4; Yang, Xing 5; Zhang, Shuixing 3; Tian, Jie 1,2,9
发表期刊	EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN	1619-7070
	2022-08-04
页码	13
通讯作者	Yang, Xing(yangxing2017@bjmu.edu.cn) ; Zhang, Shuixing(shui7515@126.com) ; Tian, Jie(jie.tian@ia.ac.cn)
摘要	Purpose Accurate identification of nodal status enables adequate neck irradiation for nasopharyngeal carcinoma (NPC). However, most conventional techniques are unable to pick up occult metastases, leading to underestimation of tumor extensions. Here we investigate the clinical significance of carbonic anhydrase IX (CAIX) in human NPC samples, and develop a CAIX-targeted imaging strategy to identify occult lymph node metastases (LNMs) and extranodal extension (ENE) in animal studies. Methods A total of 211 NPC samples are performed CAIX staining, and clinical outcomes are analyzed. The metastatic murine models are generated by foot pad injection of NPC cells, and a CAIX-targeted imaging agent (CAIX-800) is intravenously administered. We adopt fluorescence molecular tomography and ultrasonography (US)-guided spectroscopic photoacoustic (sPA) imaging to perform in vivo studies. Histological and immunohistochemical characterization are carried out via node-by-node analysis. Results For clinical samples, 90.1% (91/101) primary tumors, 73.3% (66/90) metastases, and 100% (20/20) local recurrences are CAIX positive. In metastases group, 84.7% (61/72) nodal metastases and 22.2% (4/18) organ metastases are CAIX positive. CAIX expression in primary tumors is significantly associated with NPC stage and prognosis. For animal studies, CAIX-800-based fluorescence imaging achieves 81.3% sensitivity and 93.8% specificity in detecting occult LNMs in vivo, with a minimum detectable diameter of 1.7 mm. Coupled with CAIX-800, US-guided sPA imaging could not only detect subcapsular deposits of metastatic cancer cells 2 weeks earlier than conventional techniques, but also successfully track pathological ENE. Conclusion CAIX remarkably expresses in human NPCs and stratifies patient prognosis. In preclinical studies, CAIX-800based imaging successfully identifies occult LNMs and tracks early stage of pathological ENE. This attractive method shows potential in clinic, allowing medical workers to longitudinally monitor nodal status and helping to reduce unnecessary nodal biopsy for patients with NPC.
关键词	Carbonic anhydrase IX Nasopharyngeal carcinoma Extranodal extension Occult lymph node metastasis Ultrasonography-guided spectroscopic photoacoustic imaging
DOI	10.1007/s00259-022-05922-6
关键词[WOS]	EXTRANODAL EXTENSION ; NECK CANCERS ; TUMOR-GROWTH ; LYMPH-NODES ; METASTASIS ; HEAD ; HYPOXIA ; RADIOTHERAPY ; SPECIFICITY ; SENSITIVITY
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[82027803] ; National Natural Science Foundation of China[62027901] ; National Natural Science Foundation of China[81930053] ; National Natural Science Foundation of China[81227901] ; National Natural Science Foundation of China[81871346] ; National Natural Science Foundation of China[81871323] ; National Natural Science Foundation of China[92059101] ; National Natural Science Foundation of China[21877004] ; Chinese Academy of Sciences[YJKYYQ20180048] ; Chinese Academy of Sciences[QYZDJ-SSW-JSC005] ; Excellent Member Project of Youth Innovation Promotion Association CAS[2016124] ; Project of High-Level Talents Team Introduction in Zhuhai City
项目资助者	National Natural Science Foundation of China ; Chinese Academy of Sciences ; Excellent Member Project of Youth Innovation Promotion Association CAS ; Project of High-Level Talents Team Introduction in Zhuhai City
WOS研究方向	Radiology, Nuclear Medicine & Medical Imaging
WOS类目	Radiology, Nuclear Medicine & Medical Imaging
WOS记录号	WOS:000836079200002
出版者	SPRINGER
引用统计	被引频次：1[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/173211/49831
专题	中国科学院分子影像重点实验室
通讯作者	Yang, Xing; Zhang, Shuixing; Tian, Jie
作者单位	1.Northeastern Univ, Coll Med & Biol Informat Engn, Shenyang 110057, Peoples R China 2.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, State Key Lab Management & Control Complex Syst, 95 Zhongguancun East Rd, Beijing 100190, Peoples R China 3.Jinan Univ, Affiliated Hosp 1, Med Imaging Ctr, 613 Huangpu West Rd, Guangzhou 510632, Peoples R China 4.Hainan Med Univ, Dept Radiol, Hainan Gen Hosp, Hainan Affiliated Hosp, Haikou 570311, Hainan, Peoples R China 5.Peking Univ First Hosp, Dept Nucl Med, 8 Xishiku Rd, Beijing 100034, Peoples R China 6.Univ Melbourne, Dept Chem & Biomol Engn, Melbourne, Vic 3010, Australia 7.Cornell Univ, Dept Radiol, Weill Med Coll, 407 E 61st St, New York, NY USA 8.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China 9.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Sch Engn Med, Beijing 100191, Peoples R China
第一作者单位	中国科学院自动化研究所
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	Huang, Wenhui,Wang, Kun,Huang, Weiyuan,et al. Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2022:13.
APA	Huang, Wenhui.,Wang, Kun.,Huang, Weiyuan.,He, Zicong.,Zhang, Jingming.,...&Tian, Jie.(2022).Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,13.
MLA	Huang, Wenhui,et al."Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING (2022):13.