Staging metastatic urothelial cancer with Nectin‐4 imaging using Gallium‐68‐N188 PET/CT

ObjectiveTo quantify Nectin‐4 expression in tumour lesions using the Nectin‐4‐binding peptide Gallium‐68‐N188 and positron emission tomography (PET)/computed tomography (CT) in patients with advanced or metastasised urothelial cancer eligible for therapy with the Nectin‐4‐directed antibody–drug conjugate enfortumab vedotin, in combination with checkpoint inhibitor pembrolizumab (Ev/P).MethodsIn 10 patients, Nectin‐4 PET/CT imaging was analysed before planned systemic therapy with Ev/P based on standardised uptake value (SUV) measurements and the results were correlated to available microscopic findings on Nectin‐4 immunohistochemistry and to clinical follow‐up.ResultsNectin‐4 PET is suitable for detecting Nectin‐4 expression in tumour lesions and demonstrates heterogeneity in Nectin‐4 expression – for example, between lymph node metastases and organ metastases. PET imaging of Nectin‐4 expression is therefore a potentially clinically relevant method for managing the application of Nectin‐4‐targeted therapies.ConclusionsWe show, as a proof of principle, that Nectin‐4 expression can be detected on imaging and serves as an innovative biomarker for targeted therapy in urothelial cancer. Intra‐individual heterogeneous expression of Nectin‐4 in metastatic sites is frequent.