ImmunoPET Imaging of Trop2 Expression in Bladder Cancer Using [64Cu]Cu-NOTA-Trodelvy

Abstract

Trop2 exhibits significantly elevated expression in numerous solid malignancies, playing a crucial role in tumor advancement, whereas its presence in healthy tissues is minimal. In this study, we investigated Trop2 expression in bladder cancer models using [⁶⁴Cu]Cu-NOTA-Trodelvy for immunoPET imaging. In HT-1376 models, [⁶⁴Cu]Cu-NOTA-Trodelvy effectively visualized tumor as early as 12 h p.i. (10.30 ± 1.45% ID/g), with tumor uptake increasing and peaking at 48 h p.i. (13.73 ± 1.16% ID/g), highlighting its potential for tumor imaging. Control groups also demonstrated low tumor uptake (5.27 ± 1.14% ID/g at 48 h in the blocking group; 6.33 ± 0.74% ID/g at 48 h in UM-UC-3; 4.50 ± 0.30% ID/g at 48 h in the [⁶⁴Cu]Cu-NOTA-IgG group). Long-term fluorescence imaging further confirmed the tumor uptake rate in the IRDye 800CW-Trodelvy group was significantly higher than in the IRDye 800CW-Trodelvy blockade group (P < 0.001). Our findings demonstrated that [⁶⁴Cu]Cu-NOTA-Trodelvy enables specific and prolonged tumor accumulation in bladder cancer models, providing precise and noninvasive monitoring of Trop2 expression.

Keywords: Cu-64; ImmunoPET; Trop2; antibody-drug conjugate; bladder cancer; radioactive tracer.