Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer

Ying Chen, Catherine A. Foss, Youngjoo Byun, Sridhar Nimmagadda, Mrudula Pullambhatla, James J. Fox, Mark Castanares, Shawn E. Lupold, John W. Babich, Ronnie C. Mease, Martin G. Pomper

Research output: Contribution to journalArticle

Abstract

To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[125I]iodo-benzoylamino)- pentyl]-ureido]-pentanedioic acid ([125I]3), 2-[3-[1-carboxy-5-(4- [18F]fluoro-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([ 18F]6), and 2-(3-[1-carboxy-5-[(5-[125I]iodo-pyridine-3- carbonyl)-amino]-pentyl]-ureido)-pentanedioic acid ([125I]8) in 65-80% (nondecay-corrected), 30-35% (decay corrected), and 59-75% (nondecay-corrected) radiochemical yields. Compound [125I]3 demonstrated 8.8 ± 4.7% injected dose per gram (%ID/g) within PSMA + PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. Similar tumor uptake values at early time points were demonstrated for [18F]6 (using PET) and [ 125I]8. Because of the many radiohalogenated moieties that can be attached via the ε amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.

Original languageEnglish (US)
Pages (from-to)7933-7943
Number of pages11
JournalJournal of medicinal chemistry
Volume51
Issue number24
DOIs
StatePublished - Dec 25 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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