Institutional Repository of Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing 100190, Peoples R China
| 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
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| Source Publication | EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
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| ISSN | 1619-7070 |
| 2022-08-04 | |
| Pages | 13 |
| Corresponding Author | Yang, Xing(yangxing2017@bjmu.edu.cn) ; Zhang, Shuixing(shui7515@126.com) ; Tian, Jie(jie.tian@ia.ac.cn) |
| Abstract | 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. |
| Keyword | Carbonic anhydrase IX Nasopharyngeal carcinoma Extranodal extension Occult lymph node metastasis Ultrasonography-guided spectroscopic photoacoustic imaging |
| DOI | 10.1007/s00259-022-05922-6 |
| WOS Keyword | EXTRANODAL EXTENSION ; NECK CANCERS ; TUMOR-GROWTH ; LYMPH-NODES ; METASTASIS ; HEAD ; HYPOXIA ; RADIOTHERAPY ; SPECIFICITY ; SENSITIVITY |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | 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 |
| Funding Organization | 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 Research Area | Radiology, Nuclear Medicine & Medical Imaging |
| WOS Subject | Radiology, Nuclear Medicine & Medical Imaging |
| WOS ID | WOS:000836079200002 |
| Publisher | SPRINGER |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ia.ac.cn/handle/173211/49831 |
| Collection | 中国科学院分子影像重点实验室 |
| Corresponding Author | Yang, Xing; Zhang, Shuixing; Tian, Jie |
| Affiliation | 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 |
| First Author Affilication | Institute of Automation, Chinese Academy of Sciences |
| Corresponding Author Affilication | Institute 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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