Comparative diagnostic performance of 18 F-FAPI-42 versus 18 F-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.