Gastrointestinal cancer with indeterminate 18F-FDG PET/CT findings: Diagnostic efficacy analysis of 68Ga-FAPI-04 PET/MRI.

The present prospective study aimed to investigate whether gallium-68-labeled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04) positron emission tomography (PET)/magnetic resonance imaging (MRI) could provide notably increased diagnostic accuracy, semi-quantitative parameters, staging capability, diagnostic guidance value and improved clinical benefits compared with fluorine-18-labeled fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) in gastrointestinal (GI) cancer with atypical metabolic activity (uncertain 18F-FDG imaging results). In total, 22 patients with histopathologically confirmed GI cancer, clinically suspected of recurrence or metastasis, but with atypical/inconclusive 18F-FDG PET/CT results, were analyzed. The present study planned to perform 68Ga-FAPI-04 PET/MRI within 1-4 days. The diagnostic performance of both tracers was evaluated. Tumor-to-background ratio was used to quantify the radiotracer uptake. The present study employed Fisher's exact test to statistically analyze the association between pathological subtypes and changes in tumor staging, as well as treatment decisions indicated by 68Ga-FAPI-04 PET. The results demonstrated that 68Ga-FAPI-04 had significantly higher sensitivity compared with 18F-FDG in detecting lymph node involvement (100 vs. 89.01%; P=0.001) and distant organ metastases (92.31 vs. 61.54%; P=0.008). Me 68Ga-FAPI-04 uptake was significantly higher in primary tumors [median, 6.13 (range, 5.71-7.57) vs. 2.62 (1.82-3.03); P=0.004], lymph nodes (9.07±2.93 vs. 3.96±1.73; P<0.001) and various metastatic sites (3.31±2.19 vs. 6.87±4.16; P<0.001). The findings indicated that 68Ga-FAPI-04 has potential advantages in diagnostic efficiency and visual evaluation. Furthermore, 68Ga-FAPI-04 altered staging in 36.4% (8/22) of patients and refined the treatment strategies for 27.3% (6/22), particularly those with poorly differentiated adenocarcinoma or mucinous carcinoma. For the 22 patients in the present study, the hospital cost for 68Ga-FAPI-04 PET/MRI was higher compared with that for 18F-FDG PET/CT. However, it generated overall benefits that essentially offset the additional costs. By enabling the timely detection of anastomotic recurrence, lymph node metastasis and distant metastasis for prompt intervention, it saved time, reduced the risk of further disease progression, and also minimized some unnecessary medical procedures caused by false-positive 18F-FDG results. These findings suggested that 68Ga-FAPI-04 PET/MRI is key to enhancing the diagnostic performance for 18F-FDG metabolically atypical GI tumors, refining clinical decision-making and providing economic benefits. This clinical trial was registered at Clinicaltrials.gov with ID NCT06270394 (date of registration, February 20th, 2024; retrospectively registered).