uPAR: a new ligand for PET imaging of prostate cancer?

A recent paper from a group of researchers at the Danish-Chinese Center for Proteases and Cancers in Copenhagen, Denmark describes their investigation into the potential of labelled urokinase-type plasminogen activator receptor (uPAR) as a PET ligand for use in the examination of human prostate cancer (Persson et al. Nucl Med Biol. 2013; 40: 618). uPAR is overexpressed in human prostate cancer and has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. The Danish group synthesized an N-terminal NOTA-conjugated version (NOTA-AE105) to develop the first 18F-labeled uPAR positron-emission-tomography PET ligand and investigated its role in targeting uPAR-positive prostate tumors. They found a high and specific tumor uptake. At 1h post injection, the uptake of 18F-AlF-NOTA-AE105 in PC-3 tumors was 4.22 ± 0.13%ID/g. uPAR-binding specificity was demonstrated by a reduced uptake of (18F-AlF-NOTA-AE105 after co-injection of a blocking dose of uPAR antagonist at all three time points investigated. Good tumor-to-background ratio was observed in small animal PET and confirmed in the biodistribution analysis. Ex vivo uPAR expression analysis on extracted tumors confirmed human uPAR expression that correlated close with tumor uptake of 18F-AlF-NOTA-AE105. The favorable in vivo kinetics and easy production method facilitate its future clinical translation for identification of prostate cancer patients with an invasive phenotype and poor prognosis.