Clinical evaluation of the novel FAP-targeting PET tracer 68Ga-XT117 in solid tumors, its synergistic role, and comparison with 18F-FDG

This study aimed to evaluate the diagnostic performance of the novel fibroblast activation protein-targeting PET tracer 68Ga-XT117 compared with 18F-fluorodeoxyglucose (18F-FDG) in solid tumors. This single-center, prospective, open-label study enrolled 14 patients with solid tumors. Participants received 68Ga-XT117 at different doses (3, 5, or 7 mCi) and underwent PET/CT scans at multiple time points. Image quality was assessed using maximum standardized uptake value and tumor-to-background ratio. All patients underwent both 68Ga-XT117 and 18F-FDG PET/CT within 1 week for head-to-head comparison. 68Ga-XT117 demonstrated optimal imaging quality at a dose of 5 mCi with an acquisition time of 40-min postinjection. In the head-to-head comparison, 68Ga-XT117 detected 137 lesions and 18F-FDG detected 138 lesions overall. 68Ga-XT117 showed improved detection of primary lesions (23 vs. 20) and lymph node metastases (13 vs. 6) compared to 18F-FDG. The tracer exhibited significantly higher uptake in sarcomas compared to gastrointestinal tumors (P = 0.014). Additionally, 68Ga-XT117 showed advantages in detecting certain lesion subtypes, particularly lymph node metastases, and bone lesions. The administration of 68Ga-XT117 was well tolerated, and no adverse events were observed or reported during the study. 68Ga-XT117 demonstrates favorable diagnostic performance, particularly in low-metabolic tumors, with good safety and optimal imaging characteristics. The tracer shows a complementary value to 18F-FDG in lesion detection. Further prospective studies are warranted to validate the clinical significance of the additionally detected lesions.