title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  [(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.
authors: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical School, Baltimore, Maryland, USA.
authors: Ying
authors: Y
authors: Chen
authors: Mrudula
authors: M
authors: Pullambhatla
authors: Catherine A
authors: CA
authors: Foss
authors: Youngjoo
authors: Y
authors: Byun
authors: Sridhar
authors: S
authors: Nimmagadda
authors: Srinivasan
authors: S
authors: Senthamizhchelvan
authors: George
authors: G
authors: Sgouros
authors: Ronnie C
authors: RC
authors: Mease
authors: Martin G
authors: MG
authors: Pomper
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D011874:Radiometry / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics
chemical_list: C572626:2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid; D000954:Antigens, Surface; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D014508:Urea; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D008239:Lysine