A Radiofluorinated Nanobody PET Tracer to Dynamically Visualize Differential Nectin4 Expression In Vivo

Nectin4 is a potential therapeutic target for multiple cancer types. To develop a diagnostic radiotracer for nectin4, a nanobody-based PET tracer was selected from several candidate sequences and prepared via [¹⁸F]AlF radiolabeling. The radiochemical quality was assessed, and tracer uptake was evaluated in cell lines and tumor models with varying nectin4 expression levels. In vitro and in vivo studies showed that the tracer exhibited a specific affinity for nectin4, with a binding affinity (K_D) of 6.77 nM in cell lines. The tracer enabled clear visualization of nectin4-expressing lesions, and its uptake profile and pharmacokinetic behavior were characterized using dynamic PET imaging and kinetic analysis. A correlation between PET signal intensity and histological nectin4 expression was also observed in tumor models. Thus, it may have the potential to become a nectin4 tracer for clinical applications.