5-[211 At]astato-2'-deoxyuridine, an alpha particle-emitting endoradiotherapeutic agent undergoing DNA incorporation.

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.