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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Larsen, RH; Vaidyanathan, G; Zalutsky, MR

Published Date

  • July 1997

Published In

Volume / Issue

  • 72 / 1

Start / End Page

  • 79 - 90

PubMed ID

  • 9246197

International Standard Serial Number (ISSN)

  • 0955-3002

Language

  • eng

Conference Location

  • England