2-(3-{1-Carboxy-5-[(6-[18F]Fluoro-Pyridine-3-Carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid, [18F]DCFPyL, a PSMA-Based PET Imaging Agent for Prostate Cancer

Purpose: We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[F-18]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioicacid, [F-18]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen (PSMA). PSMA is upregulated in prostate cancer epithelia and in the neovasculature of most solid tumors. Experimental Design: [F-18] DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[F-18]fluoronicotinic acid tetrafluorophenyl ester ([F-18]F-PyTFP) for introduction of F-18. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PSMA PC3 PIP and PSMA-PC3 flu xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0. Results: DCFPyL displays a K-i value of 1.1 +/- 0.1 nmol/L for PSMA. [F-18] DCFPyL was produced in radiochemical yields of 36%-53% (decay corrected) and specific radioactivities of 340-480 Ci/mmol (12.6-17.8 GBq/mu mol, n = 3). In an immunocompromised mouse model [F-18] DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39.4 +/- 5.4 percent injected dose per gramof tissue (%ID/g) was evident within the PSMA+ PC3 PIP tumor, with a ratio of 358:1 of uptake within PSMA+ PC3 PIP to PSMA- PC3 flu tumor placed in the opposite flank. At or after 1 hour postinjection, minimal nontarget tissue uptake of [F-18] DCFPyL was observed. The bladder wall is the dose-limiting organ. Conclusions: These data suggest [F-18] DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues. Clin Cancer Res; 17(24); 7645-53. (C)2011 AACR.