Transport of free ²¹¹At and ¹²⁵I⁻ in thyroid epithelial cells: effects of anion channel blocker 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid on apical efflux and cellular retention

Abstract 

Introduction

Astatine (²¹¹At; α-emitter; t_1/2=7.21 h) shares several features with its halogen neighbour iodine. In the present study, we investigated whether 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) can be used to increase the cellular retention time of ²¹¹At and radioiodide in thyroid epithelial cells.

Methods

The transepithelial transport and cellular uptake of ²¹¹At and ¹²⁵I⁻ were studied simultaneously in porcine thyrocytes cultured in bicameral chambers. The cells were prestimulated with thyroid-stimulating hormone (TSH) or epidermal growth factor (EGF) for 48 h. In addition, the acute effects of DIDS and forskolin were investigated.

Results

The transepithelial transport of both radionuclides was stimulated by TSH and down-regulated by EGF. DIDS rapidly reduced the efflux and increased the cellular content of ¹²⁵I⁻ in control and TSH-stimulated cells, whereas DIDS had no effect on ¹²⁵I⁻ transport in EGF-treated cells. DIDS blocked the ²¹¹At efflux only in TSH-stimulated cells. Unexpectedly, DIDS caused an accelerated efflux of ²¹¹At in both control and EGF-stimulated cells and, furthermore, reduced the cellular content of ²¹¹At in the EGF-stimulated cultures. DIDS had no effect on the forskolin-induced efflux of the two radionuclides.

Conclusions

The magnitude of thyroidal ²¹¹At uptake and efflux is similar to that of ¹²⁵I⁻, strongly dependent on the functional activity of the cells. However, ²¹¹At efflux likely involves several permeating mechanisms with different sensitivity to DIDS, which are at least partly not shared by ¹²⁵I⁻. The results suggest that anion channel blockage is potentially useful to increase the absorbed dose from both ²¹¹At and radioiodine in NIS-expressing tumours.

Keywords: Astatine, Iodine, Thyroid, Efflux, EGF