Radiation-induced thyroid stunning: differential effects of (123)I, (131)I, (99m)Tc, and (211)At on iodide transport and NIS mRNA expression in cultured thyroid cells.
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.


CONCLUSIONS
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.
Lundh
Charlotta
C
Department of Radiation Physics, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. charlotta.lundh@radfys.gu.se
Lindencrona
Ulrika
U
Postgård
Per
P
Carlsson
Therese
T
Nilsson
Mikael
M
Forssell-Aronsson
Eva
E
D000818:Animals; D001246:Astatine / Q000008:administration & dosage*; D001693:Biological Transport, Active / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects; D007455:Iodine / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D013552:Swine; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013667:Technetium / Q000008:administration & dosage*; D013959:Thyroid Diseases / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D001246:Astatine; D007455:Iodine; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D027981:Symporters; D013667:Technetium; D000099209:Sodium-Iodide Symporters