Beyond FDG-PET/CT-a scoping review about the diagnostic accuracy of new PET/CT tracer in patients with urothelial carcinoma
Jennifer Winkler, Emil Novruzov, Camilla M. Grunewald, Eduards Mamlins, Marc Rehlinghaus, Frederik L. Giesel, Günter NiegischBackground
Accurate staging is essential in urothelial carcinoma (UC), yet the utility of [ 18 F]FDG PET/CT (FDG) is limited by high physiologic urinary excretion, which obscures primary lesions and regional nodes. Non-FDG tracers with lower urinary clearance may improve pelvic and metastatic detection, informing treatment selection such as bladder-sparing strategies versus cystectomy.
Objectives
To map the clinical evidence on non-FDG PET tracers in UC staging and to chart their reported performance against FDG and conventional imaging.
Eligibility Criteria
In-human clinical studies reporting accuracy or lesion-detection metrics for non-FDG PET/CT in UC that used [ 18 F]FDG PET/CT as comparator, with histopathology or conventional imaging as additional reference where reported.
Sources of Evidence
MEDLINE (PubMed), Cochrane Library and Scopus, last searched 31 st August [2025]. Forty-two articles were screened, 25 met predefined inclusion criteria.
Charting Methods
Data were charted using a predefined form covering study design, population, tracer, reference standard and performance measures. Findings were grouped by tracer class. Heterogeneity was too high for meta-analysis.
Results
Six tracer classes were identified. FAPI consistently outperformed FDG, with sharper tumor-to-background contrast, up to 30 % more lesions detected and markedly higher nodal sensitivity at preserved specificity. [ 11 C]Choline and [ 11 C]acetate showed negligible urinary excretion and the highest sensitivity for primary-tumor visualization, but only modest gains over FDG for nodal or distant staging. In one prospective comparison, [ 64 Cu]CuCl 2 surpassed FDG and contrast-enhanced CT on lesion-based analysis and improved nodal specificity. PSMA ligands, [ 18 F]Fluciclovine and immuno-PET agents targeting Nectin-4 or uPAR offered target-specific benefits but were not consistently superior.
Conclusion
Evidence remains in an early validation phase. FAPI is the most consistently promising tracer, particularly for nodal staging, while choline, acetate and fluciclovine may suit selected pelvic applications. Small, heterogeneous studies with variable reference standards dominate, and head-to-head comparisons with standardized protocols and pathological validation are needed before routine use.