Comparison of ⁶⁸ Ga-NY104 PET/CT with ¹⁸ F-FDG PET/CT in patients with metastatic clear cell renal cell carcinoma (NYCRM): A prospective, comparative phase II study.

4524 Background: 68 Ga-NY104 is a small-molecule PET agent selectively targeting carbonic anhydrase IX (CAIX), which is highly expressed on clear cell renal cell carcinoma (ccRCC). This phase II study aims to evaluate the diagnostic efficacy of 68 Ga-NY104 PET/CT in patients with metastatic clear cell renal cell carcinoma and compare it with 18 F-FDG PET/CT. Methods: Patients with metastatic ccRCC were prospectively recruited in this study (ClinicalTrials.gov: NCT05879471). All participants underwent 68 Ga-NY104 and 18 F-FDG PET/CT within one week. Tyrosine kinase inhibitors were stopped at least one week before the study. Any lesion that can be detected on either PET or CT is included for further analysis. The number and uptake of lesions were recorded. The diagnostic efficacy was determined at lesion level and region level based on a comprehensive reference standard protocol. Results: Forty-four patients (mean age, 59.6 ± 10.7) were recruited, including 40 men and 4 women. A total of 677 lesions in 172 regions were identified, of which 568 lesions and 128 regions were considered positive for ccRCC based on reference standard. The lesion-level sensitivity and specificity of 68 Ga-NY104 PET/CT to detect ccRCC lesion are 96.6% (95% CI, 95.2% - 98.1%) and 99.1% (95% CI, 97.3% - 100%), which is significantly higher than that of 18 F-FDG PET/CT (sensitivity, 77.8%, 95% CI, 74.4% - 81.2%, P＜0.001; specificity, 5.5%, 95% CI, 1.2% - 9.8%, P＜0.001). The region-level sensitivity and specificity of 68 Ga-NY104 PET are 98.4% (95% CI, 96.3% - 100%) and 97.7% (95% CI, 93.3% - 100%), which is also significantly higher than that of 18 F-FDG PET/CT (sensitivity, 82.0%, 95% CI, 75.4% - 88.7%, P＜0.001; specificity, 11.4%, 95% CI, 2.0% - 20.7%, P＜0.001).The SUVmax of ccRcc lesions (n = 568) were 12.6 ± 11.7 for 68 Ga-NY104 versus 7.5 ±10.5 for 18 F-FDG (P＜0.001). The TBR is also higher (15.7 ± 14.6 v.s. 4.8 ±5.5, P＜0.001). A significant SUVmax difference between ccRCC and non-ccRCC lesion was noted for 68 Ga-NY104 (12.6 ± 11.7 v.s. 1.2 ±1.0, P＜0.001), which is not true for 18 F-FDG (7.5 ±10.5 v.s. 6.5 ±3.5, P = 0.061). Conclusions: 68 Ga-NY104 PET/CT is a promising tool with high diagnostic efficacy in patients with metastatic ccRCC. It is better than 18 F-FDG PET/CT in both sensitivity and specificity. Clinical trial information: NCT05879471 . Diagnostic efficacy of 68 Ga-NY104 and 18 F-FDG PET/CT. Sensitivity 95% CI Specificity 95% CI Lesion-level (n=677) 68Ga-NY104 96.6% 95.2%-98.1% 99.1% 97.3%-100% 18F-FDG 77.8% 74.4%-81.2% 5.5% 1.2%-9.8% Region-level (n=172) 68Ga-NY104 98.4% 96.3%-100% 97.7% 93.3%-100% 18F-FDG 82.0% 75.4%-88.7% 11.4% 2.0%-20.7%