Abstract
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Background: 211At is an alpha-emitter which has similar chemical properties to iodine and is used in targeted alpha 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).
Methods: Crude 211At solution (AA(-) solution) and 211At solution treated with AA (AA(+) solution) were prepared. Uptakes by the thyroid were compared between the two solutions in normal male Wistar rats (n = 6). Cellular uptake analysis in K1-NIS cells was performed under the AA(+) and AA(-) conditions. AA(+) solution was injected at three 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 four groups.
Results: Uptake by the thyroid was significantly enhanced in rats injected with the AA(+) solution as compared to those injected with AA(-)solution. Cellular uptake analysis showed significantly increased uptake of 211At by the K1-NIS cells under the AA(+) condition as compared to the AA(-) condition. In the mouse xenograft model, the K1-NIS tumors showed significant accumulation of 211At at 3 and 24 hr post administration (22.5± 10.4 %ID and 12.9± 6.8 %ID, 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.
Conclusions: Uptake of 211At was enhanced in differentiated thyroid cancer cells as well as the normal thyroid using 211At solution treated with AA. It also showed dose-dependent efficacy against the K1-NIS xenografts, suggesting its potential applicability to targeted alpha therapy.
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