Comparison of the diagnostic accuracy between 18F-FAPI-04 PET/CT and 18F-FDG PET/CT in the clinical stage IA of lung adenocarcinoma

Background: Fluorine 18-labeled fibroblast activation protein inhibitor (F-18-FAPI-04) positron emission tomography/computed tomography (PET/CT) has shown promise for the visualization of advanced stage lung cancer. The accuracy of F-18-FAPI-04 compared with that of fluorine-18 labeled-fluorodeoxyglucose (F-18-FDG) in detecting early lung adenocarcinoma (LUAD) remains unknown. Taking the surgical pathology of pulmonary nodule as the gold standard, the diagnostic performance of stage IA LUAD were compared between F-18-FAPI-04 PET/CT and F-18-FDG PET/CT, and the correlation between F-18-FAPI-04 uptake and pathological characteristics of stage IA LUAD. Methods: This prospective study from February 2023 to October 2023 analyzed patients with stage IA LUAD who underwent simultaneous examinations with F-18-FAPI-04 and F-18-FDG PET/CT. Semi-quantitative parameters such as maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), FAPI avid tumor volume (FTV), and total lesion FAP expression (TLF) were calculated. The two patterns were compared using either a paired Student's t-test or a Wilcoxon signed-rank test. Immunohistochemical (IHC) staining for detecting fibroblast activating protein (FAP) expression was performed in all resected tumor specimens. Correlation analysis was performed between F-18-FAPI-04 uptake and pathological features of stage IA LUAD. Results: A total of 20 patients diagnosed with stage IA LUAD were included in this study. A total of 24 pulmonary nodules were identified in these 20 patients, all of whom were confirmed to have stage IA LUAD through operation and pathology. Of them, 17 nodules were stained by FAP immunohistochemistry. Compared with F-18-FDG, F-18-FAPI-04 PET/CT showed a statistically significant increase in SUVmax and TBR for stage IA LUAD, both in the overall and stratified analyses (adenocarcinoma in situ + minimally invasive adenocarcinoma groups vs. invasive adenocarcinoma groups; moderately vs. well-differentiated lesions; stage IA1 vs. IA2+3; P<0.05). The SUVmax of the intense FAP expression group was significantly higher than that of the mild FAP expression group, demonstrating a statistically significant difference (P=0.005). The FAP-IHC score was positively correlated with the SUVmax of F-18-FAPI-04 (r=0.64, P=0.005). Conclusions: F-18-FAPI-04 PET/CT demonstrates higher SUVmax and TBR than F-18-FDG PET/CT in the detection of stage IA LUAD. It was re-assured that the F-18-FAPI-04 uptake of stage IA LUAD was positively correlated with the expression of FAP in vitro.