ImmunoPET Imaging of Nectin4 Expression in Gastric and Bladder Cancer Using [⁶⁴Cu]Cu-NOTA-Padcev

Nectin4 is a tumor-associated antigen that is highly expressed in various solid tumors and is associated with tumor progression and poor prognosis. We performed an ImmunoPET imaging study to assess Nectin4 expression in gastric and bladder cancer models utilizing [⁶⁴Cu]Cu-NOTA-Padcev. ImmunoPET imaging confirmed significant tumor uptake at 48 h in NCI-N87 (13.83 ± 1.80% ID/g) and HT-1376 (22.97 ± 2.67% ID/g) models, which was significantly higher than in HGC-27 (5.93 ± 0.15% ID/g, <i>P</i> = 0.0163) and UM-UC-3 (5.40 ± 0.69% ID/g, <i>P</i> = 0.0051) models. Co-injection of [⁶⁴Cu]Cu-NOTA-Padcev with 2 mg of unlabeled Padcev significantly decreased tumor uptake in NCI-N87 (5.53 ± 0.59% ID/g, <i>P</i> = 0.0097) and HT-1376 (4.97 ± 0.68% ID/g, <i>P</i> = 0.0049), indicating receptor-specific binding. Fluorescence imaging consistently showed significantly greater tumor accumulation in the IRDye 800CW-Padcev group than in the blocking group for both the NCI-N87 model (64.05 ± 8.97 × 10⁷ vs 10.12 ± 1.83 × 10⁷ at 168 h for the NCI-N87 model, <i>P</i> = 0.0072) and the HT-1376 model (99.48 ± 13.61 × 10⁷ vs 10.12 ± 1.83 × 10⁷ at 168 h for the HT-1376 model, <i>P</i> = 0.0068). [⁶⁴Cu]Cu-NOTA-Padcev ImmunoPET imaging demonstrated specific, rapid, and prolonged accumulation in Nectin4-high tumors in both gastric and bladder cancer models.