Preoperative evaluation of mediastinal lymph nodes in non-small cell lung cancer using [68Ga]FAPI-46 PET/CT: a prospective pilot study

Abstract Purpose Mediastinal nodal staging is crucial for surgical candidate selection in non-small cell lung cancer (NSCLC), but conventional imaging has limitations often necessitating invasive staging. We investigated the additive clinical value of fibroblast activation protein inhibitor (FAPI) PET/CT, an imaging technique targeting fibroblast activation protein, for mediastinal nodal staging of NSCLC. Methods In this prospective pilot study, we enrolled patients scheduled for surgical resection of NSCLC based on specific criteria designed to align with indications for invasive staging procedures. Patients were included when meeting at least one of the following: (1) presence of FDG-positive N2 lymph nodes, (2) clinical N1 stage, (3) central tumor location or tumor diameter of ≥ 3 cm, and (4) adenocarcinoma exhibiting high FDG uptake. [ 68 Ga]FAPI-46 PET/CT was performed before surgery after a staging workup including [ 18 F]FDG PET/CT. The diagnostic accuracy of [ 68 Ga]FAPI-46 PET/CT for “N2” nodes was assessed through per-patient visual assessment and per-station quantitative analysis using histopathologic results as reference standards. Results Twenty-three patients with 75 nodal stations were analyzed. Histopathologic examination confirmed that nine patients (39.1%) were N2-positive. In per-patient assessment, [ 68 Ga]FAPI-46 PET/CT successfully identified metastasis in eight patients (sensitivity 0.89 (0.52–1.00)), upstaging three patients compared to [ 18 F]FDG PET/CT. [ 18 F]FDG PET/CT detected FDG-avid nodes in six (42.8%) of 14 N2-negative patients. Among them, five were considered non-metastatic based on calcification and distribution pattern, and one was considered metastatic. In contrast, [ 68 Ga]FAPI-46 PET/CT correctly identified all non-metastatic patients solely based on tracer avidity. In per-station analysis, [ 68 Ga]FAPI-46 PET/CT discriminated metastasis more effectively compared to [ 18 F]FDG PET/CT-based (AUC of ROC curve 0.96 (0.88–0.99) vs. 0.68 (0.56–0.78), P < 0.001). Conclusion [ 68 Ga]FAPI-46 PET/CT holds promise as an imaging tool for preoperative mediastinal nodal staging in NSCLC, with improved sensitivity and the potential to reduce false-positive results, optimizing the need for invasive staging procedures.