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

Eur J Nucl Med Mol Imaging. 2008 Jul;35(7):1272-81. doi: 10.1007/s00259-008-0775-4. Epub 2008 Apr 11.


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 (131)I. In the current study, we studied the potential of the high-energy alpha-emitter (211)At, also transported by NIS, as an alternative radionuclide after NIS gene transfer in tumors with limited therapeutic efficacy of (131)I due to rapid iodide efflux.

Methods: We investigated uptake and therapeutic efficacy of (211)At 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 (211)At in a perchlorate-sensitive manner, which allowed a dramatic therapeutic effect in vitro. After intraperitoneal injection of (211)At (1 MBq), NP-1 tumors accumulated approximately 16% ID/g (211)At (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 (211)At has been demonstrated in prostate cancer after PSA promoter-directed NIS gene transfer in vitro and in vivo suggesting a potential role for (211)At as an attractive alternative radioisotope for NIS-targeted radionuclide therapy, in particular in smaller tumors with limited radionuclide retention time.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astatine / administration & dosage
  • Astatine / pharmacokinetics
  • Astatine / therapeutic use*
  • Cell Line, Tumor
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • Prostate-Specific Antigen / genetics
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / radiotherapy*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Symporters / genetics
  • Symporters / metabolism*
  • Transfection
  • Transplantation, Heterologous
  • Tumor Stem Cell Assay


  • Recombinant Proteins
  • Symporters
  • sodium-iodide symporter
  • Prostate-Specific Antigen
  • Astatine