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 211At emits α-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-[211At]astato-2′-deoxyuridine ([211At]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 [211At]AUdR was virtually identical to [131I]IUdR; both exhibited a linear increase in cell uptake with activity concentration, an inhibition of uptake by 10 µm IUdR, and the incorporation of about 50% of cell-bound activity into DNA. In a clonogenic assay, [211At]AUdR exhibited a high cytotoxicity for D-247 MG cells, with a D0 equivalent to less than 3 211At atoms/cell.


Supported in part by Grants CA 42324 and NS 20023 from the NIH.

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