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

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. 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 ofTc-pertechnetate and I 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. 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 Tc-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. 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.

Preoperative Use of Intravenous Contrast Media Is Associated With Decreased Excellent Response Rates in Intermediate-Risk DTC Patients Who Subsequently Receive Total Thyroidectomy and Low-Dose RAI Therapy

“…These results indicated that UI concentration within normal range cannot guarantee the absence of interference from ICM in terms of clinical outcome. This was in accordance with the theory proposed by Vassaux et al (14) in in vitro studies as mentioned previously. Therefore, our study demonstrated in a clinical practice setting that it might be not suitable for using a "normal UI concentration" to decide the initiation of RAI therapy if the patients had received preoperative ICM.…”

“…Moreover, in a recent study, Vassaux et al suggested that independent of free iodide, the ICM itself could directly reduce thyroid iodide uptake by decreasing NIS expression in thyroid cells. Besides, they found that ICM induces thyroid stunning to a greater and longer-lasting degree than free iodide found in ICM could explain (14). Thus, the influence of the use of ICM might have been stronger and more enduring than we previously thought.…”

Identification of oncolytic vaccinia restriction factors in canine high-grade mammary tumor cells using single-cell transcriptomics

“…BHK21, MCF7, MDA-MB231, HeLa and DDIT4 +/+ and -/- MEF cells were obtained and cultured as previously described [ 50 , 58 – 62 ]. Fluorescence imaging and Western blots were performed as previously described [ 63 , 64 ]. Quantification of the number of fluorescent cells as well as the intensity of fluorescence was performed using the CellQuant program (available at: http://biophytiro.unice.fr/cellQuant/index_html ).…”

<p>Improving ¹³¹I Radioiodine Therapy By Hybrid Polymer-Grafted Gold Nanoparticles</p>

“…37 Immuno-Fluorescence Experiments NIS-B16F10 cells plated in 24-well format were allowed to grow 24 hrs at 37°C and 5 % CO 2 before being fixed (2% PFA) and permeabilized (0.1% triton). After a blockade step (BSA 1%), immunofluorescence labelling was performed according to 38 using NIS Ab25, anti-mNIS is an affinity purified rabbit polyclonal antibody as previously described. 39…”

“…Iodide uptake in whole cells was performed according to 38 with 30 μM NaI and 125 I. Measurements were made after 1 hr in the presence or the absence of 100 mM perchlorate, a NIS inhibitor. The radioactivity was measured using a gamma counter (Packard Cobra).…”