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Iodinated Contrast Agents Perturb Iodide Uptake by the Thyroid Independently of Free Iodide

Iodinated Contrast Agents Perturb Iodide Uptake by the Thyroid Independently of Free Iodide

Georges Vassaux, Colette Zwarthoed, Laurie Signetti, Julien Guglielmi, Catherine Compin, Jean-Marie Guigonis, Thierry Juhel, Olivier Humbert, Danielle Benisvy, Thierry Pourcher, Béatrice Cambien

J Nucl Med. 2018 Jan;59(1):121-126.

PMID: 29051343

Abstract:

Perturbation of thyroid iodide uptake is a well-documented side effect of the use of iodinated contrast media (ICM) administered intravenously. This side effect is thought to be mediated by free iodide in ICM formulations, but this hypothesis has never been formally proven. The aim of the present study was 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. SPECT/CT was used to measure the in vivo uptake of 99mTc-pertechnetate and 123I in 2 NIS-expressing mouse tissues, thyroid and salivary glands. Scintiscans of ICM-naïve and ICM-administered patients were compared. Immunohistologic 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 was affected by ICM. The thyroid-selective effect of ICM was also observed in humans. Administration of potassium iodide as a source of free iodide led to a diminution of 99mTc-pertechnetate uptake in both mouse thyroid and mouse 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 demonstrated 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 ability of ICM to perturb iodide uptake in the thyroid may be used in radioprotection.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS72735	i-Butylammonium iodide			Price
LS72737	i-Propylammonium iodide			Price

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