Nectin-4 PET for predicting enfortumab vedotin dose-response in urothelial carcinoma.

ABSTRACT: Optimizing dosing strategies is critical to balance effectiveness and toxicity, especially for drugs with narrow therapeutic windows such as antibody-drug conjugates (ADCs). This study evaluates whether positron emission tomography (PET) imaging targeting Nectin-4 can noninvasively quantify the real-time interaction of the ADC enfortumab vedotin (EV) with tumors in urothelial carcinoma. Using the imaging agent [⁶⁸Ga]AJ647, dynamic changes in the interaction of EV with Nectin-4 were measured across preclinical models and correlated with therapeutic responses. PET imaging identified dose-dependent variations in Nectin-4 engagement, with suboptimal EV doses resulting in incomplete Nectin-4 engagement and increased tumor growth. Crucially, PET-measured target engagement predicted th

SUBMITTER: Mishra A 

PROVIDER: S-EPMC12778052 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature