[18F]FAPI adds value to [18F]FDG PET/CT for diagnosing lymph node metastases in stage I-IIIA non-small cell lung cancer: a prospective study

Background This study investigates the value of fluorine 18 ([F-18])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC). Methods From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [F-18]-fluorodeoxyglucose (FDG) and [F-18]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [F-18]FDG and [F-18]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated. Results In 53 patients (median age, 64 years, range: 31-76 years), the specificity of [F-18]FAPI for detecting LN metastasis was significantly higher than that of [F-18]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(>= 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUVmax (>= 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [F-18]FAPI in this circumstance improved the diagnostic value. LNs with an [F-18]FAPI SUVmax<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [F-18]FAPI SUVmax >= 6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [F-18]FDG and [F-18]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients. Conclusion In patients with stage I-IIIA NSCLC, [F-18]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [F-18]FDG PET/CT. Integrating [F-18]FDG and [F-18]FAPI PET/CT resulted in more precise clinical decisions.