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Radiation-Induced Thyroid Stunning: Differential Effects of ¹²³I, ¹³¹I, ^99mTc, and ²¹¹At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

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

Recent clinical and experimental data demonstrate that thyroid stunning is caused by previous irradiation and may influence the efficacy of ¹³¹I radiation therapy of thyroid cancer and possibly hyperthyroidism. To avoid stunning, many clinics have exchanged ¹³¹I for ¹²³I for pretherapeutic diagnostic imaging and dose planning. Furthermore, recent in vitro studies indicate that ¹³¹I 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 ¹²³I and ¹³¹I in addition to some other potentially interesting radionuclides. Methods: Thyrotropin-stimulated thyroid cell monolayers were exposed to 0.5 Gy of ¹²³I, ¹³¹I, ^99mTc, or ²¹¹At, all being radionuclides transported via NIS, in the culture medium for 6 h, or to various absorbed doses of ¹²³I or ¹³¹I 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 ²¹¹At, followed by ¹²³I and ^99mTc (equally potent), whereas ¹³¹I was least effective. The onset of NIS downregulation was rapid (<1 d after irradiation) in cells exposed to ¹²³I or ²¹¹At and was delayed in cells irradiated with ¹³¹I or ^99mTc. Iodide transport and NIS expression were recovered only for ²¹¹At. ¹²³I reduced the iodine transport and the NIS mRNA expression more efficiently than did ¹³¹I 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 ¹²³I than for ¹³¹I. Despite the lower absorbed dose per unit activity for ¹²³I than for ¹³¹I, stunning by ¹²³I 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 ²¹¹At (which has the highest relative biological effectiveness) causing the highest degree of stunning per unit absorbed dose in the present study.

Key Words: thyroid stunning • NIS • ¹³¹I • ¹²³I • ^99mTc • ²¹¹At

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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JNM 2009 50: 11A-12A. [Full Text]