title: 5-[211 At]astato-2'-deoxyuridine, an alpha particle-emitting endoradiotherapeutic agent undergoing DNA incorporation.
abstract: When labeled with the subcellular range Auger electron emitters 125I and 123I, the thymidine analogue 5-iodo-2'deoxyuridine (IUdR) is highly cytotoxic but only to cells going through S-phase during exposure to these radiopharmaceuticals. Since 211 At emits alpha-particles of high linear energy transfer, but with a range of a few cell diameters, an IUdR analogue labeled with 211At could markedly improve the homogeneity of tumor dose deposition. Herein we describe the synthesis of 5-[211 At]astato-2'-deoxyuridine ([211 At]AUdR) in 85-90% radiochemical yield via the astatodestannylation of 5-(trimethylstannyl)-2'-deoxyuridine. In vitro studies using the human glioma cell line D-247 MG demonstrated that [211 At]AUdR was virtually identical to [131I]IUdr; both exhibited a linear increase in cell uptake with activity concentration, an inhibition of uptake by 10 micrometers IUdR, and the incorporation of about 50% of cell-bound activity into DNA. In a clonogenic assay, [211 At]AUdR exhibited a high cytotoxicity for D-247 MG cells, with a D(0) equivalent to less than 3 211At atoms/cell.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: G
authors.initials: G
authors.lastname: Vaidyanathan
authors.forename: R H
authors.initials: RH
authors.lastname: Larsen
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D004273:DNA, Neoplasm / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D006207:Half-Life; D006801:Humans; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018499:Linear Energy Transfer; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; C098409:5-astato-2'-deoxyuridine; D007065:Idoxuridine