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

Clin Cancer Res. 2011 Dec 15;17(24):7645-53. doi: 10.1158/1078-0432.CCR-11-1357. Epub 2011 Oct 31.


Purpose: We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [(18)F]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: [(18)F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[(18)F]fluoronicotinic acid tetrafluorophenyl ester ([(18)F]F-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)F]DCFPyL 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)F]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 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)F]DCFPyL was observed. The bladder wall is the dose-limiting organ.

Conclusions: These data suggest [(18)F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Surface / metabolism
  • Cell Line, Tumor
  • Fluorine Radioisotopes
  • Glutamate Carboxypeptidase II / antagonists & inhibitors
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Lysine / analogs & derivatives*
  • Lysine / chemical synthesis
  • Lysine / pharmacokinetics
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Molecular Structure
  • Neoplasms, Experimental / diagnosis
  • Neoplasms, Experimental / diagnostic imaging
  • Neoplasms, Experimental / metabolism
  • Positron-Emission Tomography / methods*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism
  • Radiometry / methods
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution
  • Transplantation, Heterologous
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis
  • Urea / pharmacokinetics


  • 2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid
  • Antigens, Surface
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Urea
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Lysine