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Review

Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review)

  • Authors:
    • Min Wang
    • Yuqin Li
    • Wenbo Yang
    • Bin Liu
  • View Affiliations / Copyright

    Affiliations: Department of Nuclear Medicine, Suining Central Hospital, Suining, Sichuan 629000, P.R. China
  • Article Number: 153
    |
    Published online on: March 2, 2026
       https://doi.org/10.3892/ol.2026.15505
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Abstract

Clear cell renal cell carcinoma (ccRCC) is highly aggressive and exhibits significant heterogeneity, making early diagnosis challenging. Carbonic anhydrase IX (CAIX) is highly expressed in the majority of ccRCC cases while exhibiting minimal expression in normal tissues, rendering it an ideal target for molecular imaging and targeted therapy. In recent years, various CAIX‑targeted radiopharmaceuticals based on antibodies, small molecules and Affibodies have rapidly advanced in PET/SPECT imaging and targeted radionuclide therapy. Preclinical studies have demonstrated that probes labeled with 89Zr, 124I, 68Ga, 18F, 99mTc, 111In and 64Cu exhibit an excellent imaging performance and tumor specificity. Radiolabeled immunotherapies using 177Lu and 225Ac have effectively inhibited tumor growth in animal models, and early clinical studies suggest controllable safety in patients with metastatic ccRCC, although bone marrow suppression and potential nephrotoxicity remain concerns. Overall, CAIX‑targeted radiopharmaceuticals provide important avenues for early diagnosis, intraoperative localization, recurrence monitoring and personalized treatment of ccRCC. Future efforts should focus on clinical trials and dosimetry optimization to facilitate clinical translation of these agents.
View Figures

Figure 1

Pharmacokinetics of antibody-based
tracers and small-molecule probes and their impact on clinical
decision-making. In CAIX-targeted imaging of ccRCC, antibody-based
tracers and small-molecule probes exhibit distinct pharmacokinetic
profiles with important clinical implications. Antibody-based
tracers have prolonged circulation times and typically require
delayed imaging (5–7 days post-injection), resulting in high tumor
uptake and increasing tumor-to-background contrast over time, but
with relatively limited tumor penetration and higher radiation
exposure. They are primarily cleared via hepatic metabolism with
partial renal excretion. By contrast, small-molecule probes
demonstrate rapid blood clearance and enable imaging within 1–2 h
post-injection. Although predominantly renally excreted - with
potential high renal background or limited abdominal lesion
detection - they achieve high early tumor-to-nontarget contrast and
a lower overall radiation dose. Antibody-based tracers are
advantageous for precise tumor burden assessment and patient
selection for CAIX-targeted or radionuclide therapy, whereas
small-molecule probes are better suited for rapid diagnosis, early
tumor localization and staging. Tracer selection should be
individualized according to clinical context and diagnostic or
therapeutic needs. CAIX, carbonic anhydrase IX.
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Copy and paste a formatted citation
Spandidos Publications style
Wang M, Li Y, Yang W and Liu B: Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review). Oncol Lett 31: 153, 2026.
APA
Wang, M., Li, Y., Yang, W., & Liu, B. (2026). Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review). Oncology Letters, 31, 153. https://doi.org/10.3892/ol.2026.15505
MLA
Wang, M., Li, Y., Yang, W., Liu, B."Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review)". Oncology Letters 31.5 (2026): 153.
Chicago
Wang, M., Li, Y., Yang, W., Liu, B."Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review)". Oncology Letters 31, no. 5 (2026): 153. https://doi.org/10.3892/ol.2026.15505
Copy and paste a formatted citation
x
Spandidos Publications style
Wang M, Li Y, Yang W and Liu B: Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review). Oncol Lett 31: 153, 2026.
APA
Wang, M., Li, Y., Yang, W., & Liu, B. (2026). Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review). Oncology Letters, 31, 153. https://doi.org/10.3892/ol.2026.15505
MLA
Wang, M., Li, Y., Yang, W., Liu, B."Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review)". Oncology Letters 31.5 (2026): 153.
Chicago
Wang, M., Li, Y., Yang, W., Liu, B."Application of carbonic anhydrase IX‑targeted radiopharmaceuticals in the diagnosis and treatment of clear cell renal cell carcinoma (Review)". Oncology Letters 31, no. 5 (2026): 153. https://doi.org/10.3892/ol.2026.15505
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