Abstract
Triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) are aggressive solid tumors with limited treatment options. Nectin cell adhesion molecule 4 (Nectin4) is a tumor-associated antigen frequently overexpressed in these cancers, making it a promising therapeutic and imaging target. Here, we report the development and evaluation of [(89)Zr]Zr-desferrioxamine (DFO)-Padcev, a radiolabeled antibody-drug conjugate targeting Nectin4, for immuno-positron emission tomography (ImmunoPET) imaging. [(89)Zr]Zr-DFO-Padcev is synthesized with a radiochemical yield of 88.87% ± 2.59% and a radiochemical purity above 99%. ImmunoPET imaging successfully visualizes Nectin4-positive tumors in TNBC (MDA-MB-468) and NSCLC (H1975) models as early as 6 h post-injection, with uptake progressively increasing and peaking at 48 h (14.57 ± 1.94 and 9.50 ± 0.76 %ID/g, respectively). Minimal tumor uptake is observed in blocking and Nectin4-negative controls, confirming specificity. Complementary fluorescence imaging further reveals the in vivo distribution of Padcev, providing valuable insights into optimal therapeutic time windows.