Enhancement of²¹¹At Uptake via the Sodium Iodide Symporter by the Addition of Ascorbic Acid in Targeted α-Therapy of Thyroid Cancer

²¹¹At is an α-emitter that has similar chemical properties to iodine and is used in targeted α-therapy. In the present study, we added ascorbic acid (AA) to ²¹¹At solution to increase the radiochemical purity of astatide and evaluated its efficacy against differentiated thyroid cancer, which is characterized by the expression of sodium/iodide symporter (NIS). <b>Methods:</b> Crude ²¹¹At solution (AA(-)) and ²¹¹At solution treated with AA (AA(+)) were prepared. Uptake by the thyroid was compared between the 2 solutions in normal male Wistar rats (<i>n</i> = 6). Cellular uptake in K1-NIS cells was analyzed under the AA(+) and AA(-) conditions. AA(+) was injected at 3 doses into K1-NIS xenograft mice: 1 MBq (<i>n</i> = 6), 0.4 MBq (<i>n</i> = 6), and 0.1 MBq (<i>n</i> = 6), and vehicle was injected into control mice (<i>n</i> = 6). The treatment effects were compared among the 4 groups. <b>Results:</b> Uptake by the thyroid was significantly enhanced in rats injected with the AA(+) as compared with those injected with AA(-). Cellular uptake analysis showed significantly increased uptake of ²¹¹At by the K1-NIS cells under the AA(+) condition as compared with the AA(-) condition. In the mouse xenograft model, the K1-NIS tumors showed significant accumulation of ²¹¹At at 3 and 24 h after administration (22.5 ± 10.4 and 12.9 ± 6.8 percentage injected dose, respectively). Tumor growth was immediately inhibited in a dose-dependent manner after administration of ²¹¹At. In the survival analysis, the ²¹¹At groups (0.1, 0.4, and 1 MBq) showed significantly better survival than the control group. <b>Conclusion:</b> Uptake of ²¹¹At was enhanced in differentiated thyroid cancer cells as well as the normal thyroid using ²¹¹At solution treated with AA. The method also showed dose-dependent efficacy against the K1-NIS xenografts, suggesting its potential applicability to targeted α-therapy.