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Effect to Therapy of Sodium-Iodine Symporter Expression by Alpha-Ray Therapeutic Agent via Sodium/Iodine Symporter.

Kazuko Kaneda-NakashimaYoshifumi ShirakamiTadashi WatabeKazuhiro OoeTakashi YoshimuraAtsushi ToyoshimaYang WangHiromitsu HabaKoichi Fukase
Published in: International journal of molecular sciences (2022)
This study confirmed the effect of sodium/iodine symporter (NIS) expression on existing drugs by in vitro and in vivo tests using cultured cell lines. The tumor growth inhibitory effect of sodium astatide ([ 211 At]NaAt) was evaluated by in vitro and in vivo tests using human thyroid cancer cells (K1, K1/NIS and K1/NIS-DOX). NIS expression in cancer cells was controlled using the Tet-On system. [ 131 I]NaI was used as control existing drug. From the results of the in vitro studies, the mechanism of [ 211 At]NaAt uptake into thyroid cancer cells is mediated by NIS, analogous to [ 131 I]NaI, and the cellular uptake rate correlates with the expression level of NIS. [ 211 At]NaAt's ability to inhibit colony formation was more than 10 times that of [ 131 I]NaI per becquerel (Bq), and [ 211 At]NaAt's DNA double-strand breaking (DSB) induction was more than ten times that of [ 131 I]NaI per Bq, and [ 211 At]NaAt was more than three times more cytotoxic than [ 131 I]NaI (at 1000 kBq each). In vivo studies also showed that the tumor growth inhibitory effect of [ 211 At]NaAt depended on NIS expression and was more than six times that of [ 131 I]NaI per Bq.
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