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

Roswitha Runge1, Anne Naumann1, Matthias Miederer1,2

  • 1Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany.

Pharmaceuticals (Basel, Switzerland)
|April 28, 2023
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Summary

Investigating prostate cancer (PCa) treatments, this study used 5-aza-2'-deoxycitidine and valproic acid to increase prostate-specific membrane antigen (PSMA) expression. This enhanced the uptake of Lu-177-PSMA-617, improving potential radionuclide therapy efficacy.

Keywords:
5-aza-2′-deoxycitidineLNCaPLu-177–PSMA-617PC3-PSMAPSMAprostate cancervalproic acid

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Area of Science:

  • Oncology
  • Nuclear Medicine
  • Molecular Biology

Background:

  • Improving Lu-177-PSMA-617 radionuclide therapy efficacy is crucial for prostate cancer (PCa) treatment.
  • Understanding PCa progression factors can enhance targeted therapies.
  • Modulating target expression offers a potential strategy to boost therapeutic outcomes.

Purpose of the Study:

  • To investigate the stimulation of prostate cancer cell lines to increase prostate-specific membrane antigen (PSMA) expression.
  • To evaluate the impact of 5-aza-2 -deoxycitidine (5-aza-dC) and valproic acid (VPA) on PSMA expression.
  • To assess the effect of enhanced PSMA expression on the cellular uptake of Lu-177-PSMA-617.

Main Methods:

  • PC3, PC3-PSMA, and LNCaP prostate cancer cell lines were treated with varying concentrations of 5-aza-dC and VPA.
  • Cell-bound radioactivity of Lu-177-PSMA-617 was measured to determine radioligand uptake.
  • PSMA expression levels were analyzed in response to the applied substances.

Main Results:

  • Both 5-aza-dC and VPA demonstrated stimulatory effects on PSMA expression in PC3-PSMA and LNCaP cells.
  • Cellular uptake of the radioligand Lu-177-PSMA-617 significantly increased in stimulated cells.
  • PC3-PSMA cells showed approximately a 20-fold enhancement in cell-bound radioactivity compared to unstimulated controls.

Conclusions:

  • Stimulation with 5-aza-dC and VPA effectively increases PSMA expression and radioligand uptake in prostate cancer cell lines.
  • Enhanced PSMA expression holds promise for improving the efficacy of Lu-177-PSMA-617 radionuclide therapy.
  • This approach may pave the way for advanced radionuclide therapies and combination treatment strategies for prostate cancer.