Abstract
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Purpose: Astatine(211At), an alpha-emitter with similar chemical properties to iodine, is expected to have a better therapeutic effect compared to 131I (beta-emitter). In the previous study, we revealed the dose-dependent therapeutic effect of 211At-NaAt solution by K1-NIS xenograft mice. In this study, we aimed to prove the better therapeutic effect of 211At-NaAt than 131I-NaI in differentiated thyroid cancer model.
Methods: Colony assay and DNA double-strand break (DSB) assay were performed using K1-NIS (NIS-expressing human papillary thyroid cancer) cells with different activities of 131I-NaI and 211At-NaAt solutions. Biodistribution of 131I-NaI and 211At-NaAt were measured in K1-NIS xenograft mice (n=3 for each group) at 24 hours after administration. 1MBq (n=4), 4MBq (n=4) and 8MBq (twice administration of 4MBq, n=4) of 131I-NaI solution and 0.4MBq of 211At-NaAt solution (n=9) were injected to each group of K1-NIS xenograft mice. Tumor size were followed and compared.
Results: In in-vitro assay, 211At-NaAt significantly inhibited the colony formation and induced more DSBs in K1-NIS cells compared to 131I-NaI. The uptake in the tumor was higher in mice administrated with 211At-NaAt solution at 24 hours after injection. 131I-NaI solution showed tumor growth inhibition in a dose-dependent manner in the tumor xenograft model of K1-NIS. However, the effect on tumor shrinkage was minimal in 131I-NaI. 211At-NaAt solution showed better tumor-suppressive effect with longer interval for regrowth than 131I-NaI solution.
Conclusions: The 211At-NaAt induced more DSBs with better tumor-suppression effect compared to 131I-NaI in vitro and in vivo, suggesting the application of 211At-NaAt therapy for differentiated thyroid cancer instead of 131I-NaI. Figure 1. The comparison of DSB generated in K1-NIS cells between 211At-NaAt and 131I-NaI group, are expressed as the ratio of DSB in RI-treated group to control group. Figure.2. Change in the relative tumor size after administration of 131I-NaI solution. Figure 3. The comparison of relative tumor size of K1-NIS xenograft mice administrated with 4MBq 131I-NaI solution and 0.4MBq 211At-NaAt solution.
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