First-in-human ex-vivo validation of carbonic anhydrase IX-PET for high-risk renal cancer (CAT-VHL - PNRR-POC-2023-12377493)

Rationale: 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. Methods: 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. Results: 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. Conclusion: 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.