[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 ([¹⁸F])-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. [¹⁸F]-fluorodeoxyglucose (FDG) and [¹⁸F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [¹⁸F]FDG and [¹⁸F]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 [¹⁸F]FAPI for detecting LN metastasis was significantly higher than that of [¹⁸F]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 SUV_max (≥ 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 [¹⁸F]FAPI in this circumstance improved the diagnostic value. LNs with an [¹⁸F]FAPI SUV_max<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [¹⁸F]FAPI SUV_max≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [¹⁸F]FDG and [¹⁸F]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, [¹⁸F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [¹⁸F]FDG PET/CT. Integrating [¹⁸F]FDG and [¹⁸F]FAPI PET/CT resulted in more precise clinical decisions.

Trial registration: The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995 ).