A Novel PET/CT Tracer for Human Urokinase-Type Plasminogen Activator Receptor.

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.