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- [ ¹⁸F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [ ¹⁸F]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: [ ¹⁸F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[ ¹⁸F]fluoronicotinic acid tetrafluorophenyl ester ([ ¹⁸F]F-Py-TFP) for introduction of ¹⁸F. 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 Ki value of 1.1 ± 0.1 nmol/L for PSMA. [ ¹⁸F]DCFPyL was produced in radiochemical yields of 36%-53% (decay corrected) and specific radioactivities of 340-480 Ci/mmol (12.6-17.8 GBq/mmol, n = 3). In an immunocompromised mouse model [ ¹⁸F]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 [ ¹⁸F]DCFPyL was observed. The bladder wall is the dose-limiting organ. Conclusions: These data suggest [ ¹⁸F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues.