Recent clinical and experimental data demonstrate that thyroid stunning is caused by previous irradiation and may influence the efficacy of 131 I radiation therapy of thyroid cancer and possibly hyperthyroidism. To avoid stunning, many clinics have exchanged 131 I for 123 I for pretherapeutic diagnostic imaging and dose planning. Furthermore, recent in vitro studies indicate that 131 I irradiation reduces iodide uptake by downregulating the expression of the sodium iodide symporter (NIS). The rationale for this study was therefore to study effects on iodide transport and NIS messenger RNA (mRNA) expression in thyrocytes exposed to both 123 I and 131 I in addition to some other potentially interesting radionuclides. Methods: Thyrotropin-stimulated thyroid cell monolayers were exposed to 0.5 Gy of 123 I, 131 I, 99m Tc, or 211 At, all being radionuclides transported via NIS, in the culture medium for 6 h, or to various absorbed doses of 123 I or 131 I for 48 h. NIS mRNA expression was analyzed using quantitative reverse-transcriptase polymerase chain reaction. Results: Iodide transport and NIS mRNA expression were reduced by all radionuclides. At the same absorbed dose, iodide transport was reduced the most by 211 At, followed by 123 I and 99m Tc (equally potent), whereas 131 I was least effective. The onset of NIS downregulation was rapid (,1 d after irradiation) in cells exposed to 123 I or 211 At and was delayed in cells irradiated with 131 I or 99m Tc. Iodide transport and NIS expression were recovered only for 211 At. 123 I reduced the iodine transport and the NIS mRNA expression more efficiently than did 131 I at an equivalent absorbed dose, with a relative biological effectiveness of about 5. Conclusion: The stunning effect per unit absorbed dose is more severe for 123 I than for 131 I. Despite the lower absorbed dose per unit activity for 123 I than for 131 I, stunning by 123 I cannot be excluded in patients. The degree to which iodide transport capacity and NIS mRNA expression are reduced seems to be related to the biological effectiveness of the type of radiation delivering the absorbed dose to the target, with 211 At (which has the highest relative biological effectiveness) causing the highest degree of stunning per unit absorbed dose in the present study.

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