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Radioactive-iodine (RAI) therapy is typically unprevailing as anaplastic thyroid cancer (ATC) management, owing to the decrease in the endogenous sodium iodide symporter (NIS) expression. Therefore, new strategies for NIS re-induction are required to improve the efficacy of RAI therapy in ATC. In this study, we developed a novel high-throughput NIS enhancer screening platform using a dual reporter gene system to identify a potent tyrosine kinase inhibitor (TKI) and selected a new hit compound, K905-0266 TKI. The effects of K905-0266 TKI treatment was validated as RAI accumulation, changes in signalling pathway related to thyroid pathogenesis, and cytotoxicity of RAI depending on re-induction of endogenous NIS expression in ATC. Furthermore, we evaluated enhancement of NIS promoter and therapeutic efficacy of RAI in ATC tumour xenograft mice. After K905-0266 TKI treatment, the expression of endogenous NIS was significantly increased, while phosphorylated-ERK was decreased. In addition, the thyroid-metabolising protein expressions were upregulated and increased of RAI accumulation and its therapeutic effects in ATC. Moreover, K905-0266 TKI increased therapeutic efficacy of RAI in ATC tumour in vivo . In conclusion, we successfully established a novel high-throughput NIS enhancer screening platform to excavate a NIS enhancer and identified K905-0266 TKI among TKI candidates and it's proven to increase the endogenous NIS expression and therapeutic efficacy of RAI in ATC. These findings suggest that a novel high-throughput NIS enhancer screening platform is useful for selecting of NIS promoter enhancers. In addition, K905-0266 TKI can be used to re-induce endogenous NIS expression and recover RAI therapy in ATC., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

In vivo biodistribution and fate of extracellular vesicles (EVs) are still largely unknown and require reliable in vivo tracking techniques. In this study, in vivo bioluminescence imaging (BLI) using Renilla luciferase (Rluc) was developed and applied to monitoring of EVs derived from thyroid cancer (CAL-62 cells) and breast cancer (MDA-MB-231) in nude mice after intravenous administration and was compared with a dye-based labeling method for EV derived from CAL-62 cells. The EVs were successfully labeled with Rluc and visualized by BLI in mice. In vivo distribution of the EVs, as measured by BLI, was consistent with the results of ex vivo organ analysis. EV-CAL-62/Rluc showed strong signals at lung followed by liver, spleen & kidney ( P < 0.05). EV-MDA-MB-231/Rluc showed strong signals at liver followed by lung, spleen & kidney ( P < 0.05). EV-CAL-62/Rluc and EV-MDA-MB-231/Rluc stayed in animal till day 9 and 3, respectively; showed a differential distribution. Spontaneous EV-CAL-62/Rluc shown distributed mostly to lung followed by liver, spleen & kidney. The new BLI system used to show spontaneous distribution of EV-CAL-62/Rluc in subcutaneous CAL-62/Rluc bearing mice. Dye (DiR)-labeled EV-CAL-62/Rluc showed a different distribution in vivo & ex vivo compared to EV-CAL-62/Rluc. Fluorescent signals were predominately detected in the liver ( P < 0.05) and spleen ( P < 0.05) regions. The bioluminescent EVs developed in this study may be used for monitoring of EVs in vivo . This novel reporter-imaging approach to visualization of EVs in real time is expected to pave the way for monitoring of EVs in EV-based treatments., Competing Interests: CONFLICTS OF INTEREST The authors declare that no competing interests exist.