Abstract

PDT02, a peptide identified by phage display and subsequent amino acid optimization, was synthesized via solid–phase peptide synthesis and radiolabeled with gallium–68 to generate 68Ga–PDT02 for imaging urokinase–type plasminogen activator receptor (uPAR). 68Ga–PDT02 exhibited high radiochemical purity and moderate binding affinity to uPAR (KD = 531.3 nM). In vitro assays showed markedly higher uptake in uPAR–positive MKN45–huPAR cells than in A549 cells, indicative of receptor–mediated binding. In vivo PET imaging in MKN45–huPAR xenograft–bearing mice demonstrated specific tumor accumulation with a mean uptake of 2.88%ID/mL at 30 min post–injection, followed by rapid clearance from non–target tissues. Biodistribution confirmed rapid renal excretion and low retention in blood, yielding favorable tumor–to–background contrast. Collectively, these results highlight 68Ga–PDT02 as a promising uPAR–targeted PET radiotracer with favorable pharmacokinetics and imaging performance, supporting its potential utility for non–invasive visualization of uPAR expression in aggressive tumors.