Abstract
The perturbation of thyroid iodide uptake is a well-documented side effect of the utilization of iodinated contrast media (ICM) administrated intravenously. This side effect is thought to be mediated by free iodide in ICM formulations but this hypothesis has never been formally demonstrated. The aim of the present paper is to assess the validity of this hypothesis. Methods: We used mass spectrometry analysis to quantify free-iodide contamination in ICM. Established cell lines expressing the Na/I symporter (NIS) were used to quantify the effect of ICM on iodide uptake. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was used to measure the in vivo uptake of 99mpertechnetate and 123I in two NIS-expressing mouse tissues, thyroid and salivary glands. Scintigraphies of naïve and ICM-administered patients were compared. Immunohistological and western blot analyses were performed to evaluate NIS protein expression in these organs. Results: Although free iodide was present in ICM formulations, in vitro uptake of iodide by NIS-expressing cells was not significantly affected by ICM. In mice, intravenous or sublingual administration of ICM led to a reduction in radiotracer uptake by the thyroid, accompanied by a dramatic reduction in NIS protein expression in this tissue. In the salivary glands, neither radiotracer uptake nor NIS protein expression were affected by ICM. The thyroid-selective effect of ICM was also observed in humans. Administration of potassium iodide (KI) as a source of free iodide led to a diminution of 99mpertechnetate uptake in both mouse thyroid and salivary glands. Altogether, these data rule out a direct intervention of free iodide in the perturbation of thyroid uptake and suggest a direct and selective effect of ICM on the thyroid. Conclusion: We demonstrate that ICM reduce thyroid uptake of iodide independently of free iodide. This effect is due to a specific and dramatic decrease in NIS expression in thyrocytes. These data cast serious doubt on the relevance of measuring urinary iodide concentration to evaluate the delay between ICM administration and radioiodine therapy in patients with differentiated thyroid carcinoma. Finally, the property of ICM to perturb iodide uptake in the thyroid may be used in radioprotection.
- Animal Imaging
- Oncology: Endocrine
- Radionuclide Therapy
- free iodide
- iodide uptake
- iodinated contrast agents
- salivary glands
- thyroid
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.