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Adv."],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:p>\n                    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 [\n                    <jats:sup>68<\/jats:sup>\n                    Ga]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 therapeutic outcomes more reliably than either drug dose or baseline target expression. By defining effective target engagement levels needed for optimal therapeutic outcomes, PET imaging provides a clear benchmark for dosing decisions, maximizing efficacy while potentially reducing exposure to higher, toxic doses and thereby enhancing patient safety.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady1111","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T18:58:36Z","timestamp":1767812316000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Nectin-4 PET for predicting enfortumab vedotin dose-response in urothelial carcinoma"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-2540","authenticated-orcid":true,"given":"Akhilesh","family":"Mishra","sequence":"first","affiliation":[{"name":"The Russell H. 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