Novel Bifunctional PET Tracer 68Ga-DOTA-NI-FAPI-04 PET/CT in Gastrointestinal Tumors: An Exploratory Comparative Study With 18F-FDG

Purpose: This study aims to evaluate the clinical feasibility of 68 Ga-nitroimidazole-FAPI (NI-FAPI), targeting both hypoxia and fibroblast activation protein (FAP), in gastrointestinal tumors compared with 18 F-FDG PET/CT. Methods: Thirty-two patients with gastrointestinal tumors (21 for initial staging, 11 for restaging) underwent both 68 Ga-NI-FAPI and 18 F-FDG PET/CT within 1 week. Immunohistochemistry for FAP and hypoxia-inducible factor 1-alpha (HIF-1α) was performed. Semiquantitative parameters including SUV max , TBR, MTV, and total lesion FAP expression/glycolysis (TLF/TLG) were compared. Correlations between SUV max and primary tumor depth, the short diameter of involved lymph nodes, and liver metastases were analyzed. Results: Immunohistochemistry confirmed FAP expression on cancer-associated fibroblasts and HIF-1α in tumor cytoplasm. 68 Ga-NI-FAPI upgraded initial staging in 2 patients (9.52%). Among recurrent patients, its true positive rate was 100% versus 70% for 18 F-FDG. 68 Ga-NI-FAPI PET/CT demonstrated higher SUV max and TBR in primary tumors (14.06±6.26 vs. 10.04±6.53, P =0.005; 12.30±6.80 vs. 6.52±4.38, P <0.001), particularly in signet-ring cell carcinoma (SRCC). It detected more metastases than 18 F-FDG (306 vs. 263, P =0.003), with higher SUV max and TBR in involved lymph nodes, liver metastases, peritoneal metastases, and other distant metastases (all P <0.05). SUV max of 68 Ga-NI-FAPI positively correlated with primary tumor depth ( r =0.528, P =0.003), the short diameter of involved lymph nodes ( r =0.304, P =0.032), and liver metastases ( r =0.349, P =0.040). Conclusion: 68 Ga-NI-FAPI exhibits superior diagnostic performance in gastrointestinal tumors compared with 18 F-FDG, particularly in staging, SRCC evaluation, and metastasis detection. The positive correlation between tumor size and uptake supports its potential for patient selection in ligand-directed radionuclide therapy, establishing it as an effective theranostic agent for gastrointestinal tumors.