Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Abstract

Due to the high variance in available protocols on iodide-131 (¹³¹I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of ¹³¹I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T₄ concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and ^99mTc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) ¹³¹I alone was not sufficient to abolish thyroidal T₄ production, 500 µCi (18.5 MBq) ¹³¹I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high ¹³¹I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) ¹³¹I decreased serum T₄ concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. ^99mTc-pertechnetate scintigraphy revealed absence of thyroidal ^99mTc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.

Gestational hypothyroidism elicits more pronounced lipid dysregulation in mice than pre-pregnant hypothyroidism

“…In our current study, in addition to the decrease in serum TH, hepatic DIO1, a key enzyme that activates TH and converts thyroxine to triiodothyronine, is also downregulated in GH and PH groups, which matches up with previous study [34,35]. The mechanism for the regulation of SREBP1c by TH has remained controversial.…”

Imaging and targeted therapy of pancreatic ductal adenocarcinoma using the theranostic sodium iodide symporter (NIS) gene

“…LPEI has been shown to exhibit certain cytotoxic effects both in vitro and in vivo [ 37 – 41 ], though LPEI-based polyplexes have already been tested in a clinical trial for bladder cancer therapy and no adverse effects were reported [ 42 ]. Similarly, we have so far only encountered side effects from 131 I in one previous study with the objective to radioablate mouse thyroids under intentional stimulation of thyroidal radioiodide uptake [ 43 ]. Symptoms developed with a delay of seven days after radioiodide application, while in the current study, animal health deteriorated from the beginning of treatment [ 43 ].…”

Development of an athyroid mouse model using 131I ablation after preparation with a low-iodine diet

“…However, 131 I doses ranging from 1.04 to 37 MBq (28–1000 μCi) were used in previous thyroid ablation reports 21 , 24 – 26 . The 131 I ablation dose can produce systemic and local adverse effects, including weight loss, salivary gland dysfunction, tracheal damage, and breathing difficulty 32 , 33 . Higher doses tends to show higher ablation success rates, but more frequent adverse effects 34 .…”