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

Ying Chen, Mrudula Pullambhatla, Catherine A. Foss, Youngjoo Byun, Sridhar Nimmagadda, Srinivasan Senthamizhchelvan, George Sgouros, Ronnie C. Mease, Martin G. Pomper

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7645-7653
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number24
DOIs
StatePublished - Dec 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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