UROTHELIAL bladder cancer (UBC) accounts for around 90% of urinary tract malignancies and remains one of the most common cancers worldwide. Despite advances in surgery, chemotherapy, and radiotherapy, outcomes are still poor for many patients. A key challenge is that a large proportion of individuals are diagnosed at advanced stages, when treatment options are limited. This makes reliable urothelial bladder cancer detection and monitoring a pressing clinical need.
Same-day Imaging Advances Urothelial Bladder Cancer Monitoring
One promising avenue of research focuses on nectin-4, a cell adhesion molecule strongly associated with poor clinical outcomes. Nectin-4 is highly expressed in several solid tumours, including bladder cancer, and is already the therapeutic target of enfortumab vedotin (EV), an FDA-approved antibody–drug conjugate. While EV is transforming treatment for some patients, not all respond equally. Accurate, real-time imaging of nectin-4 expression is therefore essential to identify which urothelial bladder cancer patients are most likely to benefit.
Traditional immuno-PET imaging techniques use full-length antibodies. However, these circulate in the body for extended periods, often taking days to generate clear tumour images. This delays diagnosis and increases radiation exposure. Antibody fragments such as F(ab′)2 offer a more efficient alternative: they clear from the bloodstream faster, reduce immunogenicity, and enable same-day, high-contrast imaging when paired with short-lived isotopes like 64Cu.
In this study, researchers developed [64Cu]Cu-NOTA-EV-F(ab′)2, the first immuno-PET tracer derived directly from EV. In preclinical urothelial bladder cancer models, the tracer achieved rapid, specific uptake and detailed visualisation of nectin-4 expression within hours. The EV-F(ab′)2 fragments retained strong binding to nectin-4 and showed pharmacokinetics well-matched to 64Cu. This combination reduces radiation risk while improving diagnostic precision compared with traditional probes.
Challenges remain, particularly the renal accumulation of radiolabelled fragments. Future approaches such as coadministration of amino acids or pretargeting methods may help mitigate this effect.
By enabling accurate and same-day assessment of urothelial bladder cancer, nectin-4 immuno-PET imaging has the potential to transform clinical practice. It could support earlier detection, guide personalised therapy choices, and ultimately improve survival and quality of life for patients.
Reference
Huang W et al. [64Cu]Cu-NOTA-EV-F(ab’)2 Enables Same-Day Immuno-PET Imaging of Nectin-4 in Triple-Negative Breast and Urothelial Bladder Cancers. J Nucl Med. 2025;66(9):1365-71.
