CAIX-targeted PET/CT in the evaluation of clear cell renal cell carcinoma: a head-to-head comparison with [18F]FDG PET/CT.

PURPOSE: To evaluate the diagnostic performance and staging of the novel CAIX-targeted tracer [18F]AlF-NYM005 in clear cell renal cell carcinoma (ccRCC), and directly compare it with that of [18F]FDG PET/CT. METHODS: This prospective single-center trial enrolled 61 patients (41 male, 20 female; median age, 62.0 years). Participants underwent [18F]AlF-NYM005 and [18F]FDG PET/CT within one week. A composite reference standard including histopathology, follow-up, or multimodal imaging was used to define 331 lesions (35 renal, 296 metastatic). Diagnostic performance, standardized uptake value (SUV) and tumour-node-metastasis (TNM) classifications were evaluated and compared between the two tracers. RESULTS: For renal tumours, [18F]AlF-NYM005 PET/CT demonstrated significantly superior diagnostic performance to [18F]FDG (P < 0.001), with higher sensitivity (82.1% vs. 42.9%), specificity (85.7% vs. 42.9%), positive predictive value (95.8% vs. 75.0%), negative predictive value (54.5% vs. 15.8%), and accuracy (82.9% vs. 42.9%). In metastatic lesions, [18F]AlF-NYM005 detected significantly more lesions (248 vs. 156, P < 0.001), particularly in lymph nodes, pleura/peritoneum, and lung. Compared with [18F]FDG, [18F]AlF-NYM005 PET/CT consequently altered the staging/restaging of approximately one-third of patients. Quantitative analysis demonstrated higher tumour uptake (SUVmax) with [18F]AlF-NYM005 in renal tumours (11.8 vs. 3.5) and metastatic lesions (5.0 vs. 3.2), along with a higher tumour-to-liver ratio (3.9 vs. 1.6). Immunohistochemistry showed that 66.7% of samples had intermediate/strong CAIX expression, which was positively correlated with [18F]AlF-NYM005 uptake, pT stage, and WHO/ISUP grade. CONCLUSION: [18F]AlF-NYM005 PET/CT was superior to [18F]FDG in the detection of renal tumours and metastatic lesions, demonstrating higher radiotracer uptake and more accurate staging. TRIAL REGISTRATION: Chinese Clinical Trial Registry. ChiCTR2400085765, Registered 18 June 2024, retrospectively registered.