title: Cytotoxicity of alpha-particle-emitting 5-[211At]astato-2'-deoxyuridine in human cancer cells.
abstract: 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.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Larsen
authors.forename: G
authors.initials: G
authors.lastname: Vaidyanathan
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000512:Alpha Particles; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D001246:Astatine / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D007553:Isotope Labeling; D008545:Melanoma / Q000378:metabolism / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; C098409:5-astato-2'-deoxyuridine; D007065:Idoxuridine; D001246:Astatine