Comparative diagnostic performance of 18F-FAPI-42 versus 18F-FDG PET/computed tomography in detecting distant metastases of nasopharyngeal carcinoma and potential pitfalls

OBJECTIVE: This study aimed to directly compare the diagnostic performance of 18 F‑fibroblast activation protein inhibitor (FAPI)‑42 and 18 F‑fluorodeoxyglucose (FDG) PET/computed tomography (CT) for detecting distant metastases in nasopharyngeal carcinoma (NPC) and to identify potential pitfall. METHODS: In this study, 139 NPC patients (30 with distant metastases) underwent both 18 F‑FAPI‑42 and 18 F‑FDG PET/CT. Diagnostic efficacy (sensitivity, specificity, and accuracy) was evaluated on patient-based and lesion-based analyses for PET alone and integrated PET/CT. Visualization quality and semi-quantitative parameters were compared across different metastatic organs. Risk factors for metastasis were analyzed via univariate and multivariate logistic regression. RESULTS: For detecting distant metastases, 18 F‑FAPI‑42 PET alone demonstrated higher sensitivity than 18 F‑FDG PET (patient-based: 93.33% vs. 86.67%, P = 0.687; lesion-based: 95.88% vs. 93.13%, P = 0.200), but lower specificity (24.77% vs. 38.53%, P = 0.006; 16.08% vs. 33.33%, P < 0.001) and accuracy (39.57% vs. 48.92%, P = 0.035; 48.33% vs. 57.50%, P < 0.001). However, when interpreted as integrated PET/CT, both tracers achieved equivalent and high diagnostic performance, with no significant differences in sensitivity (95.88% vs. 93.47%), specificity (95.10% vs. 96.74%), or accuracy (both 95.42%). 18 F‑FAPI‑42 PET/CT provided superior visualization for bone and pleural metastases. False-positive lesions were common, with 18 F‑FAPI‑42 uptake frequently associated with benign bone/joint conditions and 18 F‑FDG uptake with lymph node inflammation. Multivariate analysis identified N-stage as the only independent risk factor for distant metastasis (odds ratio = 3.603, P = 0.006). CONCLUSION: While standalone PET shows differing profiles, integrated 18 F‑FAPI‑42 and 18 F‑FDG PET/CT provide comparable and high overall accuracy for detecting NPC distant metastases. 18 F‑FAPI‑42 offers advantages in visualizing bone and pleural metastases. High false-positive rates for both tracers necessitate careful interpretation with CT correlation. Advanced N-stage is a key predictor of metastatic disease.