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

Publisher: Springer-Verlag Berlin Country of Publication: Germany NLM ID: 101140988 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1619-7089 (Electronic) Linking ISSN: 16197070 NLM ISO Abbreviation: Eur J Nucl Med Mol Imaging Subsets: MEDLINE

Original Publication: Berlin : Springer-Verlag Berlin, 2002-

Carbonic Anhydrases*/analysis ; Carbonic Anhydrases*/metabolism ; Nasopharyngeal Neoplasms*/diagnostic imaging; Humans ; Mice ; Animals ; Carbonic Anhydrase IX/metabolism ; Nasopharyngeal Carcinoma/diagnostic imaging ; Biomarkers, Tumor/metabolism ; Prognosis ; Antigens, Neoplasm/analysis ; Lymphatic Metastasis ; Models, Animal

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-800-based 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. The schematic diagram for the study. CAIX, carbonic anhydrase IX; NPC, nasopharyngeal carcinoma; US, ultrasonography; sPA, spectroscopic photoacoustic.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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Keywords: Carbonic anhydrase IX; Extranodal extension; Nasopharyngeal carcinoma; Occult lymph node metastasis; Ultrasonography-guided spectroscopic photoacoustic imaging

EC 4.2.1.1 (Carbonic Anhydrase IX)
EC 4.2.1.1 (Carbonic Anhydrases)
0 (Biomarkers, Tumor)
0 (Antigens, Neoplasm)

Date Created: 20220804 Date Completed: 20221028 Latest Revision: 20221120

20240104

10.1007/s00259-022-05922-6

35925443