Comparison of PSMA- and CD70-targeted PET/CT in The Diagnosis of Renal Cell Carcinoma: A Retrospective Cohort and Prospective Head-to-head Study

PURPOSE: Currently, PSMA- and CD70-targeted imaging are the main focuses in the molecular imaging of RCC, but these modalities have not been compared in clinical studies. The primary outcome of this study was to compare the sensitivity of two imaging modalities in diagnosing RCC lesions and explore their diagnostic thresholds. Secondary outcomes included differences in detection rates, variations in tumor uptake, target-to-background ratios, and their practical impact on patient treatment decisions. EXPERIMENTAL DESIGN: Retrospectively, data were collected from patients with pathologically confirmed RCC who underwent PSMA-targeted ([68Ga]Ga-PSMA-11) or CD70-targeted ([68Ga]Ga-NOTA-RCCB6) PET/CT. Tumor uptake, target-to-background ratio, and lesion detection rates were compared. Another independent prospective study enrolled patients with suspected RCC who underwent both imaging modalities, comparing the sensitivity of the two methods in detecting RCC lesions and investigating diagnostic thresholds. RESULTS: The retrospective cohort included 128 patients, while the prospective study finally enrolled 36 patients. [68Ga]Ga-NOTA-RCCB6 exhibited higher sensitivity (88.7% vs. 76.1%; P < 0.001) for ccRCC, particularly for pulmonary and hepatic metastases, and exhibited higher SUVmax and TBR at the primary lesion and in pulmonary metastases. The detection rates of [68Ga]Ga-NOTA-RCCB6 and [⁶⁸Ga]Ga-PSMA-11 were both limited for nccRCC (68.8% and 63.0%, respectively). [68Ga]Ga-NOTA-RCCB6 improved the extent of lesion detection in 35% (9/26) of patients and affected treatment decisions in 15% (4/26) of patients. CONCLUSIONS: [68Ga]Ga-NOTA-RCCB6 PET/CT significantly enhanced diagnostic sensitivity for pulmonary and hepatic metastases, facilitating precise staging and treatment decision-making. Therefore, it represents a valuable complement to existing imaging modalities for ccRCC.