18F-FAPI-42 PET/CT and 18F-FDG PET/CT in patients with malignant digestive system neoplasms: a head-to-head comparative study

Purpose Radionuclide-labeled fibroblast activation protein inhibitor (FAPI) is an emerging tumor tracer. We sought to assess the uptake and diagnostic performance of ¹⁸ F-FAPI-42 PET/CT compared with simultaneous 2-deoxy-2[ ¹⁸ F]fluoro-D-glucose ( ¹⁸ F-FDG) PET/CT in primary and metastatic lesions in patients with malignant digestive system neoplasms and determine the potential clinical benefit. Procedures Forty-two patients (men = 30, women = 12, mean age = 56.71 ± 13.26 years) who underwent ¹⁸ F-FDG PET/CT and ¹⁸ F-FAPI-42 PET/CT simultaneously for diagnosis, staging, and restaging were enrolled. Quantitative data, including standardized uptake value (SUV), tumor-to-liver ratio (TLR), and tumor-to-blood pool ratio (TBR), were analyzed. Two independent readers performed a visual assessment of lesion number and location on PET/CT images. Interobserver agreement between two examinations was calculated using Cohen’s kappa (κ). Results Primary tumor locations included the liver (n = 20), stomach (n = 9), pancreas (n = 5), and intestine (n = 10). More intense ¹⁸ F-FAPI-42 uptake and higher tumor-to-background contrast were detected in most primary and metastatic lesions compared with ¹⁸ F-FDG, contributing to improved diagnostic accuracy ranging from 95.24–100%. Moreover, additional lesions showing ¹⁸ F-FAPI-42 uptake in primary, locoregional and distant metastatic lesions were visualized, especially in multiple liver and peritoneal metastases. Patient-based interobserver agreement varied from moderate to strong, with suboptimal outcomes observed in primary tumors (κ = 0.441, P  = 0.01) and preferable results derived from metastatic liver and bone lesions (κ = 1 and 0.896, both P  < 0.01). ¹⁸ F-FAPI-42 PET/CT resulted in modified treatment strategies for 40.48% (17/42) of patients, while ¹⁸ F-FDG PET/CT led to altered therapeutic regimens in only 4.8% (2/42) of patients. Conclusions In selected patients with malignant digestive system neoplasms, our study shows that ¹⁸ F-FAPI-42 PET/CT is a promising and alternative tool for assessing primary tumors and metastases and aiding staging, restaging, and decision-making, with higher uptake and better lesion visualization compared with ¹⁸ F-FDG. In addition, it may shed light into the treatment selection and response assessment for FAP-targeted therapy or immunotherapy.