The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer

Michael J. Willhauck, Bibi Rana Sharif Samani, Ingo Wolf, Reingard Senekowitsch-Schmidtke, Hans Jürgen Stark, Geerd J. Meyer, Wolfram H. Knapp, Burkhard Göke, John C. Morris, Christine Spitzweg

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Purpose: We reported recently the induction of selective iodide uptake in prostate cancer cells (LNCaP) by prostate-specific antigen (PSA) promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131I. In the current study, we studied the potential of the high-energy alpha-emitter 211At, also transported by NIS, as an alternative radionuclide after NIS gene transfer in tumors with limited therapeutic efficacy of 131I due to rapid iodide efflux. Methods: We investigated uptake and therapeutic efficacy of 211At in LNCaP cells stably expressing NIS under the control of the PSA promoter (NP-1) in vitro and in vivo. Results: NP-1 cells concentrated 211At in a perchlorate-sensitive manner, which allowed a dramatic therapeutic effect in vitro. After intrapertoneal injection of 211At (1 MBq), NP-1 tumors accumulated approximately 16% ID/g 211At (effective half-life 4.6 h), which resulted in a tumor-absorbed dose of 1,580 ± 345 mGy/MBq and a significant tumor volume reduction of up to 82 ± 19%, while control tumors continued their growth exponentially. Conclusions: A significant therapeutic effect of 211At has been demonstrated in prostate cancer after PSA promoter-directed NIS gene transfer in vitro and in vivo suggesting a potential role for 211At as an attractive alternative radioisotope for NIS-targeted radionuclide therapy, in particular in smaller tumors with limited radionuclide retention time.

Original languageEnglish (US)
Pages (from-to)1272-1281
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume35
Issue number7
DOIs
StatePublished - Jul 2008

Keywords

  • At therapy
  • Gene therapy
  • PSA promoter
  • Prostate cancer
  • Sodium iodide symporter

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Willhauck, M. J., Samani, B. R. S., Wolf, I., Senekowitsch-Schmidtke, R., Stark, H. J., Meyer, G. J., Knapp, W. H., Göke, B., Morris, J. C., & Spitzweg, C. (2008). The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging, 35(7), 1272-1281. https://doi.org/10.1007/s00259-008-0775-4