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5-[²¹¹At]Astato-2'-deoxyuridine, an -Particle-emitting Endoradiotherapeutic Agent Undergoing DNA Incorporation¹

Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710

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 -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.

¹ Supported in part by Grants CA 42324 and NS 20023 from the NIH.

² To whom requests for reprints should be addressed, at Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-7708; Fax: (919) 684-7121.

Received 12/ 7/95. Accepted 1/31/96.

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