This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foss, C. A. Articles by Pomper, M. G. Search for Related Content PubMed PubMed Citation Articles by Foss, C. A. Articles by Pomper, M. G.

Radiolabeled Small-Molecule Ligands for Prostate-Specific Membrane Antigen: In vivo Imaging in Experimental Models of Prostate Cancer

Authors' Affiliations: ¹ Johns Hopkins University, Baltimore, Maryland; ² Georgetown University, Washington, District of Columbia; ³ The Cleveland Clinic Foundation, Cleveland, Ohio; and ⁴ University of Illinois at Chicago, Chicago, Illinois

Requests for reprints: Martin G. Pomper, Department of Radiology, Johns Hopkins University, 600 North Wolfe Street, Phipps B-100, Baltimore, MD 21287-2182. Phone: 410-955-2789; Fax: 410-614-1213; E-mail: mpomper{at}jhmi.edu.

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_i, 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[¹²⁵I]iodo-L-tyrosine ([¹²⁵C]DCIT K_i, 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.

Key Words: PET • PSMA • imaging • prostate cancer • xenografts

This article has been cited by other articles:

				B. L. Franc, P. D. Acton, C. Mari, and B. H. Hasegawa Small-Animal SPECT and SPECT/CT: Important Tools for Preclinical Investigation J. Nucl. Med., October 1, 2008; 49(10): 1651 - 1663. [Abstract] [Full Text] [PDF]

				R. C. Mease, C. L. Dusich, C. A. Foss, H. T. Ravert, R. F. Dannals, J. Seidel, A. Prideaux, J. J. Fox, G. Sgouros, A. P. Kozikowski, et al. N-[N-[(S)-1,3-Dicarboxypropyl]Carbamoyl]-4-[18F]Fluorobenzyl-L-Cysteine, [18F]DCFBC: A New Imaging Probe for Prostate Cancer Clin. Cancer Res., May 15, 2008; 14(10): 3036 - 3043. [Abstract] [Full Text] [PDF]

				W. He, H. Wang, L. C. Hartmann, J.-X. Cheng, and P. S. Low In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry PNAS, July 10, 2007; 104(28): 11760 - 11765. [Abstract] [Full Text] [PDF]