Novel radiopharmaceuticals for bladder cancer evaluation

Molecular imaging of bladder cancer (BC) remains challenging, mainly due to the limitations of [¹⁸F]FDG PET/CT in assessing the primary tumor site and differentiating malignant from physiological urinary activity. Consequently, the development of novel PET radiopharmaceuticals is crucial to enhance diagnostic accuracy and optimize patient management. Emerging radiopharmaceuticals have shown potential advantages in this context. Therefore, the aim of this narrative review was to summarize available evidence on the role of alternative PET radiopharmaceuticals for the evaluation of BC.

Fourteen studies involving 158 patients from six countries met the inclusion criteria. Investigated radiopharmaceuticals included [¹⁸F]/[⁶⁸Ga]-FAPI, [¹⁸F]Fluciclovine, [⁶⁸Ga]Ga-N188 (nectin-4-targeted), and ⁶⁴CuCl2. In four studies, [¹⁸F]FDG PET/CT was used as an imaging comparator. The quality was good in 6 original articles including more than 10 patients. [¹⁸F]Fluciclovine demonstrated high specificity and a favorable biodistribution for muscle invasive BC staging; PSMA-targeted imaging showed diagnostic and theranostic promise despite variable expression. FAPI radiopharmaceuticals offered a superior lesion detection, image contrast, and potential therapeutic applications, while ⁶⁴CuCl2 and [⁶⁸Ga]Ga-N188 underscored a shift toward personalized molecular imaging.

Fourteen studies evaluated emerging radiopharmaceuticals for BC imaging. FAPI agents showed the highest lesion detectability, while fluciclovine demonstrated high specificity for muscle-invasive disease. PSMA tracers, ⁶⁴CuCl2 and [⁶⁸Ga]Ga-N188 underscored a growing move toward personalised, theranostic molecular imaging.

[¹⁸F]FDG remains the reference PET agent in BC; however, novel agents show encouraging results for improving staging and therapy monitoring. Broader clinical implementation requires multicentric validation and standardized imaging protocols.