⁶⁸Ga-Labeled Inhibitors of Prostate-Specific Membrane Antigen (PSMA) for Imaging Prostate Cancer

Gallium-68 is a generator-produced radionuclide for positron emission tomography (PET) that is being increasingly used for radiolabeling of tumor-targeting peptides. Compounds [⁶⁸Ga]3 and [⁶⁸Ga]6 are high-affinity urea-based inhibitors of the prostate-specific membrane antigen (PSMA) that were synthesized in decay-uncorrected yields ranging from 60% to 70% and radiochemical purities of more than 99%. Compound [⁶⁸Ga]3 demonstrated 3.78 ± 0.90% injected dose per gram of tissue (%ID/g) within PSMA+ PIP tumor at 30 min postinjection, while [⁶⁸Ga]6 showed a 2 h PSMA+ PIP tumor uptake value of 3.29 ± 0.77 %ID/g. Target (PSMA+ PIP) to nontarget (PSMA− flu) ratios were 4.6 and 18.3, respectively, at those time points. Both compounds delineated tumor clearly by small animal PET. The urea series of imaging agents for PSMA can be radiolabeled with ⁶⁸Ga, a cyclotron-free isotope useful for clinical PET studies, with maintenance of target specificity.