(S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging

In an effort to seek novel agents targeting prostate-specific membrane antigen (PSMA), 16 ligands (L1-L16) with structural modifications in S1' binding pocket were synthesized and evaluated for PSMA inhibition. (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acids proved to be potent PSMA ligands with K-i values ranging from 0.08 nM to 8.98 nM, which are in the range of or are higher in potency compared to previously published urea-based ligands. Computational docking was performed to study the binding mode of the two most potent ligands discovered. FITC-conjugated L14 could selectively stain PSMA(+) LNCaP cells over PSMA(-) PC3 cells. IRDye800CW conjugated L16 can effectively image tumors in a murine xenograft model of prostate cancer.