Radiolabeled small-molecule ligands for prostate-specific membrane antigen: In vivo imaging in experimental models of prostate cancer

Catherine A. Foss, Ronnie C. Mease, Hong Fan, Yuchuan Wang, Hayden T Ravert, Robert F. Dannals, Ratal T. Olszewski, Warren D. Heston, Alan P. Kozikowski, Martin G. Pomper

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

Abstract

Purpose: Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer, including hormone-refractory and metastatic disease. Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use. Experimental Design: We have synthesized and evaluated the in vivo biodistribution of two radiolabeled urea derivatives that have high affinity for PSMA in severe combined immunodeficient mice harboring MCF-7 (breast, PSMA-negative), PC-3 (prostate, PSMA-negative), and LNCaP (prostate, PSMA-positive) xenografts. Radiopharmaceutical binding selectivity and tumor uptake were also evaluated in vivo using dedicated small animal positron emission tomography, single photon emission computed tomography, and gamma scintigraphic imaging devices. N-[N-[(S)-1,3-dicarboxypropyl] carbamoyl]-S-[11C]methyl-L-cysteine ([11C]DCMC K j, 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3- [125I]iodo-L-tyrosine ([125C]DCIT Kj, 1.5 nmol/L) were synthesized using [11C]CH3I and with [ 125I]NaI/Iodogen, respectively. Results: At 30 minutes postinjection, [11C]DCMC and [125I]DCIT showed tumor/muscle ratios of 10.8 and 4.7, respectively, with clear delineation of LNCaP-derived tumors on imaging. MCF-7- and PC-3-derived tumors showed significantly less uptake of [11C]DCMC or [125I]DCIT. Conclusion: These results show the feasibility of imaging PSMA-positive prostate cancer using low molecular weight agents.

Original languageEnglish (US)
Pages (from-to)4022-4028
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number11
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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