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Reduced Iodide Transport (Stunning) and DNA Synthesis in Thyrocytes Exposed to Low Absorbed Doses from ¹³¹I In Vitro

¹ Department of Radiation Physics, Göteborg University, Göteborg, Sweden; and ² Department of Medical Chemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden

Correspondence: For correspondence or reprints contact: Charlotta Lundh, Department of Radiation Physics, Sahlgrenska University Hospital, Göteborg University, SE-413 45 Göteborg, Sweden. E-mail: charlotta.lundh{at}radfys.gu.se

Thyroid stunning refers to reduced uptake of ¹³¹I in the thyroid tissue (or tumor) during radioiodine (¹³¹I) therapy compared with the uptake measured after the previous administration of ¹³¹I for diagnostic purposes. The phenomenon is clinically important, as it can potentially lead to the undertreatment of thyroid cancer or to unnecessarily high absorbed doses in critical organs. Previous clinical and experimental studies indicated that thyroid stunning is absorbed dose dependent. The aim of this study was to investigate the effects of ¹³¹I irradiation on ¹²⁵I^– transport and cell proliferation at low absorbed doses in vitro. Methods: Primary cultured porcine thyroid cells were grown to form a confluent monolayer of epithelial cells on a filter in a bicameral culture system. The cells were continuously irradiated with ¹³¹I in the culture medium for 48 h to obtain 0.0015–1.5 Gy. At 3 d after irradiation was stopped, the transepithelial iodide transport capacity was evaluated by measuring ¹²⁵I^– transport from the basal chamber compartment to the apical chamber compartment. The effect of ¹³¹I irradiation on DNA synthesis was estimated by pulse labeling with ³H-thymidine of both subconfluent and confluent cells irradiated with up to 9 Gy. Total DNA content was measured to quantify cell numbers. Results: A statistically significant reduction in ¹²⁵I^– transport was seen at absorbed doses of 0.15 Gy, with a 50% reduction at 1.5 Gy, compared with the results observed for nonirradiated control cells. ³H-Thymidine incorporation was already statistically significantly reduced at absorbed doses of 0.01–0.1 Gy, but 0.15–0.3 Gy did not affect DNA synthesis. However, absorbed doses of 1 Gy again resulted in reduced DNA synthesis. A 50% reduction was obtained at 4 Gy. Total DNA measurements revealed a statistically significant reduction in cell numbers at 8 Gy. Conclusion: The lowest absorbed dose from ¹³¹I that reduced iodide transport was 0.15 Gy. Because stunning was found at low absorbed doses, it might occur for ¹³¹I treatment not only of thyroid cancer but also of thyrotoxicosis. On the basis of differences in dose responses, radiation-induced thyroid stunning and cell cycle arrest may be independent phenomena.

Key Words: thyroid • radioiodine • ¹³¹I • stunning • iodide transport • dosimetry

^* Contributed equally to this work.

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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