Abstract
Astatine ((211)At) is an alpha-emitter with a better treatment efficacy against differentiated thyroid cancer compared with iodine ((131)I), a conventional beta-emitter. However, its therapeutic comparison has not been fully evaluated. In this study, we compared the therapeutic effect between [(211)At]NaAt and [(131)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 [(211)At]NaAt (0.4 MBq (n = 7), 0.8 MBq (n = 9), and 1.2 MBq (n = 4)), and [(131)I]NaI (1 MBq (n = 4), 3 MBq (n = 4), and 8 MBq (n = 4)). The [(211)At]NaAt induced higher numbers of DSBs and had a more reduced colony formation than [(131)I]NaI. In K1-NIS mice, dose-dependent therapeutic effects were observed in both [(211)At]NaAt and [(131)I]NaI. In [(211)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 [(211)At]NaAt, respectively. While in [(131)I]NaI, this was observed within 12 days after injection (1, 3, and 8 MBq). The superior therapeutic effect of [(211)At]NaAt suggests the promising clinical applicability of targeted alpha therapy using [(211)At]NaAt in patients with differentiated thyroid cancer refractory to standard [(131)I]NaI treatment.