TY - JOUR
T1 - Radiolabeled small-molecule ligands for prostate-specific membrane antigen
T2 - In vivo imaging in experimental models of prostate cancer
AU - Foss, Catherine A.
AU - Mease, Ronnie C.
AU - Fan, Hong
AU - Wang, Yuchuan
AU - Ravert, Hayden T.
AU - Dannals, Robert F.
AU - Olszewski, Ratal T.
AU - Heston, Warren D.
AU - Kozikowski, Alan P.
AU - Pomper, Martin G.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-04-2690
DO - 10.1158/1078-0432.CCR-04-2690
M3 - Article
C2 - 15930336
AN - SCOPUS:20344374435
VL - 11
SP - 4022
EP - 4028
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 11
ER -