In vitro cytotoxicity of (211)at-astatide and (131)I-iodide to glioma tumor cells expressing the sodium/iodide symporter

J Nucl Med. 2003 Nov;44(11):1827-38.


The sodium/iodide symporter (NIS) has been identified as an attractive target for cancer therapy. The efficacy of (131)I-iodide for NIS-expressing tumor therapy may be limited by a combination of poor cellular retention and unfavorable physical characteristics (long physical half-life and low linear-energy-transfer [LET] radiative emissions). On the other hand, (211)At-astatide is also transported by NIS and offers several therapeutic advantages over (131)I-iodide due to its physical characteristics (short half-life, high LET alpha-particle emissions). The objective of this study was to directly compare the radiotoxicity of both radionuclides using a NIS-transfected cultured cell model.

Methods: Cytotoxicity was determined by colony-forming assays. Also, a first-order pharmacokinetic model was used to simulate the closed compartmental system between the medium and cells. Experimental data were then fitted to this model and used to estimate the transfer coefficients between medium and cells, k(m)(c), and between cells and medium, k(c)(m). Using the pharmacokinetic model, the cumulated activity concentrations in the medium and cells were calculated. Monte Carlo transport methods were then used to assess absorbed doses from (131)I and (211)At.

Results: (211)At-Astatide was significantly more cytotoxic than (131)I-iodide in this closed compartmental system. For (211)At-astatide, absorbed doses per unit administered activity were 54- to 65-fold higher than for (131)I-iodide. Both NIS-expressing and control cells showed increased sensitivity to (211)At over (131)I, with significantly lower D(0) (absorbed dose required to reduce the survival fraction to e(-1)) and SF(2) (2-Gy survival fraction) values, highlighting the higher intrinsic cytotoxicity of alpha-particles. However, NIS-independent (nonspecific) binding of (211)At-astatide was higher than that of (131)I-iodide, therefore, yielding a lower absorbed dose ratio between NIS-transfected and -nontransfected cells.

Conclusion: Treatment of NIS-expressing cells with (211)At-astatide resulted in higher absorbed doses and increased cytotoxicity per unit administered activity than that observed with (131)I-iodide. These results suggest that (211)At-astatide may be a promising treatment strategy for the therapy of NIS-expressing tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Astatine / pharmacokinetics
  • Astatine / therapeutic use*
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Glioma / pathology
  • Glioma / radiotherapy*
  • Humans
  • Iodine Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / therapeutic use*
  • Radiation Dosage
  • Symporters / genetics
  • Symporters / physiology*
  • Tissue Distribution
  • Transfection


  • Iodine Radioisotopes
  • Symporters
  • sodium-iodide symporter
  • Astatine