Diagnostic Accuracy of [ 68 Ga]Ga-FAP-2286 PET/CT for Various Cancer and Head-to-head Comparison to Conventional [ 18 F]F-FDG PET/CT: A Real-World, Single-Center Study

<title>Abstract</title> <p> Purpose This study aims to evaluate the diagnostic performance of fibroblast activation protein (FAP) targeted positron emission tomography/computed tomography (PET/CT) across various cancer types and to compare it with conventional [ ¹⁸ F]F-fluorodeoxyglucose ([ ¹⁸ F]F-FDG) PET/CT in a single-center, real-world cohort. Methods This single-center retrospective study included 304 patients with pathologically confirmed malignant tumors who underwent gallium (Ga) [ ⁶⁸ Ga]Ga-FAP-2286 and [ ¹⁸ F]F-FDG PET/CT scans sequentially within a 7-day period. Diagnostic accuracy was assessed at both the per-patient and per-lesion levels, with the reference standard based on histopathological findings and imaging follow-up results. Uptake parameters were compared between the two tracers. Results A total of 304 patients with various tumor types were analyzed. Compared with [ ¹⁸ F]F-FDG PET/CT, [ ⁶⁸ Ga]Ga-FAP-2286 PET/CT demonstrated higher sensitivity (99.5% vs. 93.1%) and accuracy (99.3% vs. 94.1%) at the patient level in primary tumors, and the target-to-background ratio (TBR) of [ ⁶⁸ Ga]Ga-FAP-2286 was significantly higher (7.1 ± 4.1 vs. 4.8 ± 2.8, p &lt; 0.001), particularly in hepatocellular carcinoma and pancreatic cancer. For lymph nodes and distant metastases, [ ⁶⁸ Ga]Ga-FAP-2286 detected more lesions and demonstrated higher sensitivity and accuracy, particularly for liver, pleural or peritoneal and bone metastases. However, [ ¹⁸ F]F-FDG PET/CT remained more sensitive in the detection of lung metastases (84.3% vs. 63.9%). [ ⁶⁸ Ga]Ga-FAP-2286 PET/CT ultimately led to an upgrade in the staging of distant metastases in 17 patients and an upgrade in lymph nodes staging in 44 patients. Conclusion [ ⁶⁸ Ga]Ga-FAP-2286 PET/CT outperforms [ ¹⁸ F]F-FDG PET/CT in detecting primary tumors and most metastatic sites, offering complementary advantages in staging and patient management. These findings support its use as a complementary imaging tool and highlight its potential for guiding FAP-targeted theragnostic approaches. </p>