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Up-Regulation of PSMA Expression In Vitro as Potential Application in Prostate Cancer Therapy

Affiliation
Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany
Runge, Roswitha;
Affiliation
Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany
Naumann, Anne;
Affiliation
Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany
Miederer, Matthias;
Affiliation
Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany
Kotzerke, Joerg;
Affiliation
Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany
Brogsitter, Claudia

Possibilities to improve the therapeutic efficacy of Lu-177–PSMA-617 radionuclide therapy by modulation of target expression are being investigated. Knowledge on regulatory factors that promote prostate cancer (PCa) progression may contribute to targeting prostate cancer more effectively. We aimed at the stimulation of PCa cell lines using the substances 5-aza-2′-deoxycitidine (5-aza-dC) and valproic acid (VPA) to achieve increased prostate-specific membrane antigen (PSMA) expression. PC3, PC3-PSMA, and LNCaP cells were incubated with varying concentrations of 5-aza-dC and VPA to investigate the cell-bound activity of Lu-177–PSMA-617. Stimulation effects on both the genetically modified cell line PC3-PSMA and the endogenously PSMA-expressing LNCaP cells were demonstrated by increased cellular uptake of the radioligand. For PC3-PSMA cells, the fraction of cell-bound radioactivity was enhanced by about 20-fold compared to that of the unstimulated cells. Our study reveals an increased radioligand uptake mediated by stimulation for both PC3-PSMA and LNCaP cell lines. In perspective of an enhanced PSMA expression, the present study might contribute to advanced radionuclide therapy approaches that improve the therapeutic efficacy, as well as combined treatment options.

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