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Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy
Huang, Wenhui1,2,3; Wang, Kun2; Huang, Weiyuan4; He, Zicong3; Zhang, Jingming5; Zhang, Bin3; Xiong, Zhiyuan6; Gillen, Kelly McCabe7; Li, Wenzhe8; Chen, Feng4; Yang, Xing5; Zhang, Shuixing3; Tian, Jie1,2,9
Source PublicationEUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN1619-7070
2022-08-04
Pages13
Corresponding AuthorYang, Xing(yangxing2017@bjmu.edu.cn) ; Zhang, Shuixing(shui7515@126.com) ; Tian, Jie(jie.tian@ia.ac.cn)
AbstractPurpose 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.
KeywordCarbonic anhydrase IX Nasopharyngeal carcinoma Extranodal extension Occult lymph node metastasis Ultrasonography-guided spectroscopic photoacoustic imaging
DOI10.1007/s00259-022-05922-6
WOS KeywordEXTRANODAL EXTENSION ; NECK CANCERS ; TUMOR-GROWTH ; LYMPH-NODES ; METASTASIS ; HEAD ; HYPOXIA ; RADIOTHERAPY ; SPECIFICITY ; SENSITIVITY
Indexed BySCI
Language英语
Funding ProjectNational 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
Funding OrganizationNational 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 Research AreaRadiology, Nuclear Medicine & Medical Imaging
WOS SubjectRadiology, Nuclear Medicine & Medical Imaging
WOS IDWOS:000836079200002
PublisherSPRINGER
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/49831
Collection中国科学院分子影像重点实验室
Corresponding AuthorYang, Xing; Zhang, Shuixing; Tian, Jie
Affiliation1.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
First Author AffilicationInstitute of Automation, Chinese Academy of Sciences
Corresponding Author AffilicationInstitute of Automation, Chinese Academy of Sciences
Recommended Citation
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.
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