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

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.

RESULTS

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.

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.