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

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.