Head-to-head Intra-individual Comparison of [⁶⁸Ga]-FAPI and [¹⁸F]-FDG PET/CT in Patients with Bladder Cancer

Fibroblast activation protein-(FAP)-ligands, a novel class of tracers for PET/CT imaging, demonstrated promising results in previous studies in various malignancies compared to standard [¹⁸F]FDG PET/CT. ⁶⁸Ga-labeled fibroblast activation protein inhibitor-([⁶⁸Ga]Ga-DOTA-FAPI)-PET/CT impresses with sharp contrasts in terms of high tumor uptake and low background noise leading to clear delineation. [¹⁸F]FDG PET/CT has limited accuracy in bladder cancer due to high background signal. Therefore, we sought to evaluate the diagnostic potential of [⁶⁸Ga]FAPI in patients with bladder cancer.

This retrospective analysis consisted of 8 patients (median age 66), 7 of whom underwent both [⁶⁸Ga]FAPI and [¹⁸F]FDG PET/CT scans with a median time interval of 5 days (range 1-20 days). Quantification of tracer uptake was determined with SUV_max and SUV_mean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUV_max of tumor lesions by the SUV_max of adipose tissue, skeletal muscle, and blood pool.

Overall, 31 metastases were detected in five patients including lymph node metastases (n = 23), bone metastases (n = 4), lung metastases (n = 3), and a peritoneal metastasis (n = 1). In one patient, [⁶⁸Ga]FAPI demonstrated significant uptake in the primary tumor located in the bladder wall. [⁶⁸Ga]FAPI-PET/CT demonstrated significantly higher uptake compared to [¹⁸F]FDG PET/CT with higher mean SUV_max (8.2 vs. 4.6; p = 0.01). Furthermore, [⁶⁸Ga]FAPI detected additional 30% (n = 9) lesions, missed by [¹⁸F]FDG. TBR demonstrated favorable uptake for [⁶⁸Ga]FAPI in comparison to [¹⁸F]FDG. Significant differences were determined with regard to metastasis/blood pool ([⁶⁸Ga]FAPI 5.3 vs [¹⁸F]FDG 1.9; p = 0.001).

[⁶⁸Ga]FAPI-PET/CT is a promising diagnostic radioligand for patients with bladder cancer. This first described analysis of FAP-ligand in bladder cancer revealed superiority over [¹⁸F]FDG in a small patient cohort. Thus, this so far assumed potential has to be confirmed and extended by larger and prospective studies.