Comparison of the Therapeutic Effects of [211At]NaAt and [131I]NaI in an NIS-expressing Thyroid Cancer Mouse Model

Abstract

Purpose Compared to a conventional beta-emitter 131I, an alpha-emitter 211At can have a stronger treatment effect against differentiated thyroid cancer. However, its therapeutic advantage has not been fully elucidated. Thus, here, we compared the therapeutic effect of [211At]NaAt with that of [131I]NaI. Methods In vitro observation of double-stranded breaks (DSBs) and colony formation assays were performed in K1-NIS cells. The biodistribution of [131I]NaI and [211At]NaAt was measured in K1-NIS xenograft mice at 3 and 24 h (n=12). The treatment effect was compared between [131I]NaI and [211At]NaAt in K1-NIS xenograft mice using different radioactivities for each solution (1 (n=4), 4 (n=4), and 8 MBq (n=4) of [131I]NaI and 0.4 (n=7), 0.8 (n=9), and 1.2 MBq (n=4) of [211At]NaAt).Results 211At caused more DSBs in K1-NIS cells and had a greater inhibitory effect on colony formation than 131I. In K1-NIS xenograft mice, the uptake of [131I]NaI in the thyroid gland was significantly higher than that of [211At]NaAt. In other organs and tumours, the uptake of [211At]NaAt was significantly higher than that of [131I]NaI. While both [211At]NaAt and [131I]NaI showed dose-dependent therapeutic effects, [211At]NaAt showed a stronger tumour-suppressive effect. Tumour regrowth was suppressed until 18, 25, and 46 days after 0.4, 0.8, and 1.2 MBq [211At]NaAt administration, respectively, whereas it was observed within 0–12 days after [131I]NaI administration (1, 4, and 8 MBq).Conclusions The stronger tumour-suppressive effect of [211At]NaAt solution supports the promising clinical application of [211At]NaAt therapy in patients with iodine-avid thyroid cancer refractory to [131I]NaI treatment.