Potential value of [68Ga]Ga-FAPI-46 PET in patients with metastatic urothelial carcinoma: a bi-centric analysis

Abstract Purpose [ 68 Ga]Ga-FAPI-46 has shown promise for urothelial cancer (UC) detection. This study evaluates its diagnostic value versus contrast-enhanced CT (ceCT) and 2-[ 18 F]FDG PET in the largest bi-centric cohort to date. Methods Patients with metastatic UC undergoing [ 68 Ga]Ga-FAPI-46 PET at University Hospitals Munich or Essen were retrospectively reviewed. Detection rates were compared with ceCT on a regional basis (primary, lymph nodes, visceral organs, bone). SUV max and SUV mean of two index lesions were recorded. In a sub-cohort, [ 68 Ga]Ga-FAPI-46 and 2-[ 18 F]FDG PET were compared on a lesion basis. Clinical follow-up and/or histopathology served as reference. Results Thirty-four patients underwent [ 68 Ga]Ga-FAPI-46 PET/CT and ceCT, including 10 (29%) with additional 2-[ 18 F]FDG PET/CT. Across 98 lesions ( n = 65 regions), [ 68 Ga]Ga-FAPI-46 PET detected n = 96 (98%) and ceCT n = 88 (90%), with mismatch findings in eight lymph nodes (PET positive/ceCT negative) and two visceral organs (ceCT positive/PET negative). In the subgroup comparison, 78 lesions were detected in total ([ 68 Ga]Ga-FAPI-46: n = 72 (92%); 2-[ 18 F]FDG: n = 78 (100%)). Tumour uptake was comparable (SUV max [ 68 Ga]Ga-FAPI-46 PET vs. 2-[ 18 F]FDG: 10.2 (IQR, 1.9) vs. 8.0 (IQR, 3.3), p = 0.249), whereas [ 68 Ga]Ga-FAPI-46 provided higher tumour-to-background ratios (Tumour-to-liver: 12.7 (IQR, 10.3) vs. 3.8 (IQR, 1.9), p = 0.046; tumour-to-spleen: 8.4 (IQR, 6.6) vs. 4.6 (IQR, 0.6), p = 0.016). Conclusion [ 68 Ga]Ga-FAPI-46 PET demonstrated higher regional detection rates than ceCT in UC patients, particularly for lymph node metastases. Compared to 2-[ 18 F]FDG, it provided superior tumour-to-background contrast but detected slightly fewer lesions. [ 68 Ga]Ga-FAPI-46 PET may complement established imaging in selected scenarios, although its role in routine UC staging remains investigational.