Development of a 64Cu-labelled cyclic peptide for PET imaging of urokinase plasminogen activator receptor (uPAR) in melanoma

Urokinase-type plasminogen activator receptor (uPAR) is a glycosyl-phosphatidylinositol-anchored glycoprotein on the surface of various cell types that serves to bind the urokinase plasminogen activator and localize the activation reactions in the proteolytic cascade system of plasminogen activation. Increased expression of uPAR is involved in tumor progression in breast cancer, bladder cancer, gastric cancer, and colorectal cancer. uPAR contributes to tumor invasion and metastasis, and is a prognostic factor, particularly in colorectal cancer. PET ligands targeting uPAR have been developed for tumor imaging; however, their clinical translation has been limited due to insufficient stability and S/N ratio. In this study, we aimed to develop a cyclic peptide radioligand [64Cu]N3-PEG3-WX360-Nle for PET imaging of uPAR expression in melanoma (Fig. 1).