Cytotoxicity of alpha-particle-emitting 5-[211At]astato-2'-deoxyuridine in human cancer cells

Int J Radiat Biol. 1997 Jul;72(1):79-90. doi: 10.1080/095530097143563.


This study was performed to determine the cytotoxicity of alpha-particle-emitting 5-[211At]astato-2-deoxyuridine (i.e. [211At]AUdR) for monolayers of D-247 MG human glioma cells and SK-MEL-28 human melanoma cells. Cells in exponential growth were exposed to varying activity concentrations of [211At]AUdR and for comparison [211At]astatide and the Auger electron-emitting analogue, 5-[125I]iodo-2'-deoxyuridine (i.e. [125I]IUdR). Cell uptake, DNA binding and clonogenic survival as a function of activity concentration in the medium were determined following 2 and 20-h incubations. None of the survival curves had detectable shoulders, an observation consistent with high-LET effects. The A37 (initial activity concentration yielding 37% cell survival) were significantly lower for both cell lines following 20-h exposure of [211At]AUdR than [211At]astatide. After correcting for effects from non-cell-associated activity in the medium, the specific cytotoxicity of cell-associated and DNA-bound [211At]AUdR was estimated. In the 20-h incubation experiments, the A37 for DNA-associated [211At]AUdR corresponded to about one 211At atom bound per cell for both cell lines. Unlike [211At]AUdR, there was a biphasic survival response to [125I]IUdR, consistent with the lower fractional uptake of [125I]IUdR at higher activity concentrations. These studies suggest that [211At]AUdR warrants further evaluation as an endoradiotherapeutic agent for the treatment of rapidly proliferating cancers.

Publication types

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

MeSH terms

  • Alpha Particles*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Astatine / pharmacology*
  • DNA, Neoplasm / metabolism
  • Glioma / metabolism
  • Glioma / radiotherapy*
  • Humans
  • Idoxuridine / analogs & derivatives*
  • Idoxuridine / chemical synthesis
  • Idoxuridine / pharmacokinetics
  • Idoxuridine / pharmacology
  • Iodine Radioisotopes / therapeutic use
  • Isotope Labeling
  • Melanoma / metabolism
  • Melanoma / radiotherapy*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • DNA, Neoplasm
  • Iodine Radioisotopes
  • 5-astato-2'-deoxyuridine
  • Idoxuridine
  • Astatine