Enhancement of 211At Uptake via the Sodium Iodide Symporter by the Addition of Ascorbic Acid in Targeted α-Therapy of Thyroid Cancer

At-211 is an alpha-emitter that has similar chemical properties to iodine and is used in targeted alpha-therapy. In the present study, we added ascorbic acid (AA) to At-211 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). Methods: Crude At-211 solution (AA(-)) and At-211 solution treated with AA (AA(1)) were prepared. Uptake by the thyroid was compared between the 2 solutions in normal male Wistar rats (n = 6). Cellular uptake in K1-NIS cells was analyzed under the AA(1) and AA(-) conditions. AA(1) was injected at 3 doses into K1-NIS xenograft mice: 1 MBq (n = 6), 0.4 MBq (n = 6), and 0.1 MBq (n = 6), and vehicle was injected into control mice (n = 6). The treatment effects were compared among the 4 groups. Results: Uptake by the thyroid was significantly enhanced in rats injected with the AA(1) as compared with those injected with AA(-). Cellular uptake analysis showed significantly increased uptake of At-211 by the K1-NIS cells under the AA(1) condition as compared with the AA(-) condition. In the mouse xenograft model, the K1-NIS tumors showed significant accumulation of At-211 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 At-211. In the survival analysis, the At-211 groups (0.1, 0.4, and 1 MBq) showed significantly better survival than the control group. Conclusion: Uptake of At-211 was enhanced in differentiated thyroid cancer cells as well as the normal thyroid using At-211 solution treated with AA. The method also showed dose-dependent efficacy against the K1-NIS xenografts, suggesting its potential applicability to targeted alpha-therapy.