Carbonic Anhydrase IX (CAIX) positron emission tomography (PET) is an accurate and non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma (ccRCC) but evidence in the setting of high-risk renal cancer is lacking. We conducted an exploratory investigation to integrate whole-body CAIX-PET imaging with tissue-level validation and to assess the potential impact of CAIX-PET on systemic staging in patients diagnosed with high-risk renal cancer.
Patients with cT3-cT4 or cN1 renal cancer scheduled for surgery underwent PET/CT imaging after intravenous administration of 37 MBq ±10% of [89Zr]Zr-girentuximab. Whole-body in-vivo was performed 5 ± 2 days following radiopharmaceutical injection, and surgical resection was planned 14 ± 2 days following radiopharmaceutical injection. Resected specimens were subsequently analyzed ex vivo using dedicated preclinical PET/CT imaging and correlated with histopathology and CAIX immunohistochemistry.
No adverse events following [89Zr]Zr-girentuximab administration were recorded and the procedure was deemed non-relevant in terms of radiation exposure for the surgical team. At in-vivo imaging, CAIX-PET resulted positive in 2 patients with clear cell renal cell carcinoma and negative in 1 patient with chromophobe renal cell carcinoma. At ex-vivo imaging, images overlap allowed for the assessment of spatial co-localization of regions with increased radiopharmaceutical uptake and high expression of CAIX at immunohistochemistry. In 1 patient, focal uptake in the fourth rib at CAIX-PET was confirmed as metastatic ccRCC. In 1 patient, suspicious lymph nodes at standard imaging without PET uptake were negative at final pathology.
Our findings generate the hypothesis that CAIX-PET might yield crucial information on cancer aggressiveness and systemic staging with potential key diagnostic, therapeutic and prognostic implications for patients with high-risk renal cancer.
Theranostics. 2026 May 18*** epublish ***
Alessandro Larcher, Fabrizia Gelardi, Lidija Antunovic, Annarita Savi, Michela Olivieri, Paolo Rainone, Martina Sollini, Rosa Maria Moresco, Chiara Re, Francesco Cei, Federico Belladelli, Giacomo Musso, Lucia Salerno, Francesco De Cobelli, Nazario Tenace, Maurilio Ponzoni, Antonio Cigliola, Paolo Verze, Roberto Bertini, Alberto Briganti, Francesco Montorsi, Umberto Capitanio, Andrea Salonia, Arturo Chiti
Department of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, Italy., Vita-Salute San Raffaele University, Milan, Italy., Department of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology, AOU San Giovanni di Dio Ruggi d'Aragona, Salerno, Italy.