Background/Objectives: Clear-cell renal cell carcinoma (ccRCC) represents the predominant histologic subtype of renal cancer and poses persistent diagnostic challenges, particularly in the evaluation of small renal masses, where conventional imaging and biopsy have relevant limitations. Molecular imaging targeting carbonic anhydrase IX (CAIX) has emerged as a promising non-invasive alternative. This narrative review aims to summarize the biological rationale, diagnostic performance, and potential clinical applications of [89Zr]Zr-girentuximab positron emission tomography-computed tomography (girentuximab PET-CT) in ccRCC, as well as to discuss its current limitations and future directions. Methods: A narrative synthesis of published phase 1-3 clinical trials, post hoc analyses, and early clinical series evaluating girentuximab PET-CT was performed, focusing on diagnostic accuracy, clinical impact in localized and metastatic disease, and emerging theranostic applications. Results: The phase 3 ZIRCON trial demonstrated high diagnostic accuracy of girentuximab PET-CT for indeterminate renal masses ≤7 cm, with a sensitivity of 85% and specificity of 87%, as well as performance exceeding 96% for lesions <2 cm. Early studies suggest that this modality may influence clinical decision-making by supporting active surveillance, avoiding biopsy, and refining surgical or ablative strategies, although evidence remains limited by small cohorts and lack of long-term outcome data. Exploratory data indicate improved lesion detection in metastatic ccRCC, but the absence of systematic histopathologic confirmation restricts routine staging use. Conclusions: Girentuximab PET-CT is a highly accurate, CAIX-targeted molecular imaging technique with the potential to transform the diagnostic pathway of ccRCC. While current evidence supports its use in selected localized settings, broader clinical adoption will require prospective validation of its impact on patient outcomes and management strategies.
Diagnostics (Basel, Switzerland). 2026 Apr 28*** epublish ***
Daniel A González-Padilla, Felipe Villacampa-Auba, Jorge Caño-Velasco, José Daniel Subiela, María Rodríguez, Carlos Yánez, Andrés Calva, Vanessa Talavera, Carmina Muñoz, Marcos Torres, Guillermo Barbas, Guillermo Andrés, Daniel Sánchez-Zalabardo, Edgar Fernando Guillén-Valderrama, Bernardino Miñana-López
Department of Urology, Kidney and Bladder Cancer Unit, Clínica Universidad de Navarra, 28027 Madrid, Spain., Department of Urology, Kidney and Bladder Cancer Unit, Clínica Universidad de Navarra, 31008 Pamplona, Spain., Department of Urology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, 28034 Madrid, Spain., Department of Nuclear Medicine, Clínica Universidad de Navarra, 28027 Madrid, Spain.