CAIX-targeted PET/CT in clear cell renal cell carcinoma: a systematic review of current evidence and clinical perspectives

BACKGROUND: Carbonic anhydrase IX (CAIX)-targeted PET/CT is an emerging molecular imaging approach for clear cell renal cell carcinoma (ccRCC). This systematic review aimed to summarize the clinical evidence on CAIX-targeted PET/CT for ccRCC detection and characterization. METHODS: PubMed/MEDLINE, Embase, and the Cochrane Library were searched on March 29, 2026, according to PRISMA 2020. Original clinical studies evaluating CAIX-targeted PET/CT in adult patients with suspected or confirmed renal masses or metastatic/recurrent renal cell carcinoma were included. Study selection, data extraction, and QUADAS-2 quality assessment were performed independently by two reviewers. Because of substantial clinical and methodological heterogeneity, a narrative synthesis was performed. RESULTS: Zr-girentuximab derivatives, provided the most established evidence for localized or indeterminate renal masses, showing high specificity and encouraging diagnostic accuracy for ccRCC. Small-molecule tracers enabled same-day imaging and showed promising results in metastatic disease assessment, particularly for extra-renal lesions. Performance was influenced by tracer class, imaging timing, renal background activity, lesion site, endpoint definition, and completeness of histological verification. The main methodological concerns involved patient selection, reference standard, and flow/timing domains. CONCLUSIONS: CAIX-targeted PET/CT is a promising imaging strategy for ccRCC, with antibody-based tracers currently better supported for indeterminate renal masses and small-molecule tracers emerging for metastatic disease assessment. Further prospective multicenter validation and standardized endpoints are required. The review was not registered and received no external funding.