Radiohalogenated Prostate-Specific Membrane Antigen (PSMA)-Based Ureas as Imaging Agents for Prostate Cancer

To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[I-125]iodobenzoylamino)-pentyl]-ureido]-pentanedioic acid ([I-125]3), 2-[3-[1-carboxy-5-(4-[F-18]fluoro-benzoylamino)-pentyl-ureido]-pentanedioic acid ([F-18]6), and 2-(3-[1-carboxy-5-[(5-[I-125]iodo-pyridine-3-carbonyl)-amino]-pentyl ureido)-pentanedioic acid ([I-125]8) in 65-80% (nondecay-corrected), 30-35% (decay corrected), and 59-75% (nondecay-corrected) radiochemical yields. Compound [I-125]3 demonstrated 8.8 +/- 4.7% injected close per gram (%ID/g) within PSMA(+) PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. similar tumor uptake values at early time points were demonstrated for [F-18]6 (using PET) and [I-125]8. Because of the many radiohalogenated moieties that call be attached via the e amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.