This study aimed to investigate the diagnostic efficacy of [⁶⁸Ga]Ga-NYM046 PET/CT in animal models and patients with clear cell renal cell carcinoma (ccRCC) and to compare its performance with that of ¹⁸F-FDG PET/CT. Methods: The in vivo biodistribution of [⁶⁸Ga]Ga-NYM046 was evaluated in mice bearing OS-RC-2 xenografts. Twelve patients with ccRCC were included in the study; all completed paired [⁶⁸Ga]Ga-NYM046 PET/CT and ¹⁸F-FDG PET/CT. The diagnostic efficacies of these 2 PET tracers were compared. Moreover, the positive rate of carbonic anhydrase IX in the pathologic tissue sections was compared with the SUV_max obtained by PET/CT. Results: The tumor accumulation of [⁶⁸Ga]Ga-NYM046 at 1 h after injection in OS-RC-2 xenograft tumor models was 7.21 ± 2.39 injected dose per gram of tissue. Apart from tumors, the kidney and stomach showed high-uptake distributions. In total, 9 primary tumors, 96 involved lymph nodes, and 147 distant metastases in 12 patients were evaluated using [⁶⁸Ga]Ga-NYM046 and ¹⁸F-FDG PET/CT. Compared with ¹⁸F-FDG PET/CT, [⁶⁸Ga]Ga-NYM046 PET/CT detected more primary tumors (9 vs. 1), involved lymph nodes (95 vs. 92), and distant metastases (137 vs. 127). In quantitative analysis, the primary tumors’ SUV_max (median, 13.5 vs. 2.4; z = –2.668, P = 0.008) was significantly higher in [⁶⁸Ga]Ga-NYM046 PET/CT. Conversely, the involved lymph nodes’ SUV_max (median, 5.9 vs. 7.6; z = –3.236, P = 0.001) was higher in ¹⁸F-FDG PET/CT. No significant differences were found for distant metastases (median SUV_max, 5.0 vs. 5.0; z = –0.381, P = 0.703). Higher [⁶⁸Ga]Ga-NYM046 uptake in primary tumors corresponded to higher expression of carbonic anhydrase IX, with an R² value of 0.8274. Conclusion: [⁶⁸Ga]Ga-NYM046 PET/CT offers a viable strategy for detecting primary tumors, involved lymph nodes, and distant metastases in patients with ccRCC.

本研究旨在探讨 [⁶⁸Ga]Ga-NYM046 PET/CT 在动物模型和透明细胞肾细胞癌 （ccRCC） 患者中的诊断效能，并将其性能与 ¹⁸F-FDG PET/CT 进行比较。方法： 在携带 OS-RC-2 异种移植物的小鼠中评价 [⁶⁸Ga]Ga-NYM046 的体内生物分布。该研究包括 12 例 ccRCC 患者;均已完成配对 [⁶⁸Ga]Ga-NYM046 PET/CT 和 ¹⁸F-FDG PET/CT。比较了这 2 种 PET 示踪剂的诊断效果。此外，将病理组织切片中碳酸酐酶 IX 的阳性率与 PET/CT 获得的 SUV_max 进行比较。结果： OS-RC-2 异种移植肿瘤模型中注射后 1 h [⁶⁸Ga]Ga-NYM046 的肿瘤积累为 7.21 ± 2.39 注射剂量/克组织。除肿瘤外，肾脏和胃表现出高摄取分布。使用 [⁶⁸Ga]Ga-NYM046 和 18 F-FDG PET/CT 评估了 12 例患者的 9 例原发性肿瘤、96 例累及淋巴结和 ¹⁴⁷例远处转移。与 ¹⁸F-FDG PET/CT 相比，[⁶⁸Ga]Ga-NYM046 PET/CT 检测到更多的原发性肿瘤 （9 vs. 1），涉及淋巴结 （95 vs. 92） 和远处转移 （137 vs. 127）。在定量分析中，原发肿瘤的 SUV_最大值（中位数，13.5 vs. 2.4;z = –2.668，P = 0.008）在 [⁶⁸Ga]Ga-NYM046 PET/CT 中显着升高。相反，受累淋巴结的 SUV_最大值（中位数，5.9 vs. 7.6; z = –3.236，P = 0.001）在 ¹⁸F-FDG PET/CT 中较高。 未发现远处转移的显著差异（中位 SUV max，5.0 vs. 5.0;z = –0.381，P = 0.703）。 原发性肿瘤中较高的 [⁶⁸Ga]Ga-NYM046 摄取对应于碳酸酐酶 IX 的较高表达，R² 值为 0.8274。结论：[⁶⁸Ga]Ga-NYM046 PET/CT 为检测 ccRCC 患者的原发肿瘤、受累淋巴结和远处转移提供了一种可行的策略。