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

PURPOSE: We have synthesized and evaluated in vivo 2- (3-1-carboxy-5- (6-[ (18) Ffluoro-pyridine-3-carbonyl) -amino]-pentyl-ureido) -pentanedioic acid, (18) FDCFPyL, 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: (18) FDCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C (O) -glu urea precursor using 6- (18) Ffluoronicotinic acid tetrafluorophenyl ester ( (18) FF-Py-TFP) for introduction of (18) F. 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. (18) FDCFPyL was produced in radiochemical yields of 36%-53% (decay corrected) and specific radioactivities of 340-480 Ci/mmol (12. 6-17. 8 GBq/μmol, n = 3). In an immunocompromised mouse model (18) FDCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39. 4 ± 5. 4 percent injected dose per gram of 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 (18) FDCFPyL was observed. The bladder wall is the dose-limiting organ. CONCLUSIONS: These data suggest (18) FDCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues.