89Zr-girentuximab PET/CT Enables Noninvasive Assessment of Indeterminate Renal Masses and Metastatic Clear-Cell Renal Cell Carcinoma

Background: Indeterminate renal masses (IRMs) frequently require biopsy for characterization and often lead to unnecessary surgical interventions. 89Zr-girentuximab is a positron emission tomography (PET) radiopharmaceutical targeting carbonic anhydrase IX, a biomarker overexpressed in clear-cell renal cell carcinoma (ccRCC). This real-world experience demonstrates the impact of 89Zr-girentuximab PET on the clinical management of patients with IRM and its role in differentiating primary and metastatic ccRCC from other etiologies. Methods: This prospective single-center study, part of an expanded access program (NCT06090331), investigated patients with IRM on conventional imaging who underwent 89Zr-girentuximab PET/computed tomography (PET/CT). Qualitative and quantitative PET/CT features of each lesion were assessed. Pathologic or clinical diagnosis was determined for all lesions. Referring physicians were surveyed to evaluate the impact of PET on patient management. Results: Seven male patients (age range, 57–78 years) were included; four had ccRCC (including two with metastatic disease) and three had oncocytoma (including one with Birt-Hogg-Dubé syndrome). Across all 32 lesions identified, 89Zr-girentuximab PET/CT accurately characterized each lesion based on pathologic or clinical diagnosis. 89Zr-girentuximab PET/CT identified ccRCC tumor thrombi in the inferior vena cava and renal vein branches (SUVmax 12.0–13.0), a perinephric deposit (SUVmax 36.4), and intramuscular (SUVmax 103.0), pulmonary (SUVmax 4.0–10.5), and osseous (SUVmax 10.2) metastases. 89Zr-girentuximab PET/CT enabled the diagnosis of oncocytomatosis in one patient and detected a renal lesion with positive uptake that was occult on MRI. According to referring physicians, 89Zr-girentuximab PET/CT changed clinical management in six of seven patients and improved patient care in all cases. Conclusions: 89Zr-girentuximab PET/CT provides a noninvasive tool for characterizing indeterminate renal masses and metastatic ccRCC and may improve clinical problem-solving in complex scenarios.