[68Ga]Ga-FAPI-46 PET/CT of Patients with Gastrointestinal Stromal Tumors in Comparison to 2-[18F]FDG PET/CT and Contrast-Enhanced CT: Results from a Prospective Observational Study.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Although contrast-enhanced CT (ceCT) and 2-[18F]FDG PET/CT remain standard imaging modalities, both exhibit limitations in detecting small peritoneal metastases and tumors with low metabolic activity. 68Ga-labeled fibroblast activation protein inhibitors (FAPIs) have shown promising results in various malignancies; however, comparative data on GISTs are limited. This study aimed to assess the diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT in comparison with 2-[18F]FDG PET/CT and ceCT, including evaluation of interreader reproducibility and clinical impact. Methods: This study retrospectively reviewed 25 patients with histopathologically confirmed GISTs undergoing [68Ga]Ga-FAPI-46 PET/CT as part of a prospective observational study (NCT04571086). All patients (n = 25) underwent additional clinical 2-[18F]FDG PET/CT; ceCT was performed for 23 of 25 patients. Imaging was assessed per patient and per region (primary tumor, lymph nodes, and visceral and bone metastases), and a composite reference standard that included histopathology, follow-up imaging, and clinical data was applied. Interreader agreement, stratified by experience level, was analyzed using Cohen κ (κCohen). Referring physicians completed questionnaires before and after imaging to determine clinical impact. Results: In total, 28 validated regions (n = 20 patients) were included in the diagnostic efficacy analysis. Per region, ceCT and [68Ga]Ga-FAPI-46 PET/CT demonstrated comparable sensitivity (83% vs. 81%), followed by 2-[18F]FDG PET/CT (65%). [68Ga]Ga-FAPI-46 PET/CT demonstrated the highest region-based positive predictive value (100%). The liver tumor-to-background ratio was significantly higher for [68Ga]Ga-FAPI-46 PET/CT than for 2-[18F]FDG PET/CT (median, 7.6 vs. 5.9; P = 0.034), whereas overall tumor uptake showed no significant difference. Changes in clinical management attributable to [68Ga]Ga-FAPI-46 PET/CT were observed for 6 of 24 patients (25%), including 1 major change. Interreader agreement for [68Ga]Ga-FAPI-46 PET/CT varied with reader experience, showing the highest concordance between high- and intermediate-experience readers (κCohen = 0.87 per patient and 0.47-1.00 across regions), whereas comparisons involving less experienced readers yielded lower agreement (κCohen = 0.00-0.60). Conclusion: [68Ga]Ga-FAPI-46 PET/CT demonstrated diagnostic sensitivity comparable to ceCT and superior to 2-[18F]FDG PET/CT for patients with GISTs. High diagnostic performance, especially in hepatic and peritoneal metastases, and relevant clinical impact support a role for [68Ga]Ga-FAPI-46 PET/CT as complementary imaging modality.