Fibroblast activation Protein-Targeted PET/CT using 18 FFAP-2286 for the evaluation of lung cancer: A comparative study with 18 FFDG PET/CT

FAP-2286, which is a novel cyclic peptide that targets fibroblast activation protein (FAP), demonstrates enhanced plasma stability and improved receptor selectivity compared with small-molecule FAP inhibitors (FAPIs). Although 18 FFAP-2286 exhibits benefits due to the favorable characteristics of fluorine-18-labeled tracers, its diagnostic performance in lung cancer remains to be fully elucidated. This study aimed to compare the diagnostic efficacy of 18 FFAP-2286 PET/CT with that of 18 FFDG PET/CT in lung cancer patients. Thirty patients with suspected lung cancer (18 men and 12 women; median age: 64 years IQR: 35-81) underwent both 18 FFAP-2286 and 18 FFDG PET/CT for initial staging (n = 27) or the detection of recurrence (n = 3). Diagnostic performance was assessed using histopathology and clinical follow-up as reference standards. The quantitative analysis included the maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Compared with 18 FFDG, 18 FFAP-2286 PET/CT significantly increased the TBR in primary tumors (11.60 ± 6.02 vs. 5.80 ± 3.08; P < 0.001), whereas the SUVmax was not significantly different (15.20 ± 8.25 vs. 13.81 ± 7.73; P = 0.524). Although 18 FFAP-2286 PET/CT demonstrated a lower detection rate for metastatic lymph nodes (67.46% 85/126 vs. 86.51% 109/126; P < 0.001), it exhibited a higher true positive rate (95.29% vs. 68.81%; P < 0.001). For distant metastases, 18 FFAP-2286 PET/CT demonstrated superior detection of bone (98.80% vs. 72.46%) and brain lesions (100% vs. 72.73%). Compared with 18 FFDG, 18 FFAP-2286 PET/CT demonstrates superior performance for detecting bone metastases and provides more accurate N and M staging. These findings suggest that 18 FFAP-2286 PET/CT may serve as a valuable alternative for the comprehensive evaluation of lung cancer patients.