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

Astatine (At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine (I), a conventional beta-emitter. However, its therapeutic comparison has not been fully evaluated. In this study, we compared the therapeutic effect between [At]NaAt and [I]NaI. In vitro analysis of a double-stranded DNA break (DSB) and colony formation assay were performed using K1-NIS cells. The therapeutic effect was compared using K1-NIS xenograft mice administered with [At]NaAt (0.4 MBq (n = 7), 0.8 MBq (n = 9), and 1.2 MBq (n = 4)), and [I]NaI (1 MBq (n = 4), 3 MBq (n = 4), and 8 MBq (n = 4)). The [At]NaAt induced higher numbers of DSBs and had a more reduced colony formation than [I]NaI. In K1-NIS mice, dose-dependent therapeutic effects were observed in both [At]NaAt and [I]NaI. In [At]NaAt, a stronger tumour-growth suppression was observed, while tumour regrowth was not observed until 18, 25, and 46 days after injection of 0.4, 0.8, and 1.2 MBq of [At]NaAt, respectively. While in [I]NaI, this was observed within 12 days after injection (1, 3, and 8 MBq). The superior therapeutic effect of [At]NaAt suggests the promising clinical applicability of targeted alpha therapy using [At]NaAt in patients with differentiated thyroid cancer refractory to standard [I]NaI treatment.