Development of F-Labeled Vinyl Sulfone-PSMAi Conjugates as New PET Agents for Prostate Cancer Imaging.

Radiolabeled prostate-specific membrane antigen (PSMA) ligands have been rapidly adopted as part of patient care for prostate cancer. In this study, a new series of F-labeled PSMA-targeting agents was developed based on the high-affinity Glu-ureido-Lys scaffold and F-vinyl sulfones (VSs), the tumor uptake and tumor/major organ contrast of which could be tuned by pharmacokinetic linkers within the molecules. In particular, F-PEG-VS-PSMAi showed the highest tumor uptake (12.1 ± 2.2%ID/g at 0.5 h p.i.) and F-PEG-VS-PSMAi showed the highest tumor-to-liver ratio (T/L = 3.7 ± 1.0, 4.8 ± 1.2, and 6.3 ± 1.1 at 0.5, 1.5, and 3 h p.i. respectively). Significantly, compared with the FDA-approved Ga-PSMA-11, the newly developed F-PEG-VS-PSMAi has an almost double tumor uptake ( < 0.0001) when tested in the same animal model. In conclusion, F-VS-labeled PSMA ligands are promising PET agents with prominent tumor uptake and high contrast. The lead agents F-PEG-VS-PSMAi and F-PEG-VS-PSMAi warrant further evaluation in prostate cancer patients.