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

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 (SUV_max 12.0-13.0), a perinephric deposit (SUV_max 36.4), and intramuscular (SUV_max 103.0), pulmonary (SUV_max 4.0-10.5), and osseous (SUV_max 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. <b>Conclusions:</b>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.