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BACKGROUND: Up to now, there is no unified conclusion on the selection of animals and drug doses and the criteria for successful modeling in the modeling process of hypothyroid animal models. OBJECTIVE: To explore the feasibility and optimal dose of radioactive 131I in the establishment of hypothyroidism model in rats METHODS: Forty healthy male Sprague-Dawley rats were randomly divided into five groups (n=8 per group). Four groups were injected intraperitoneally with 4.625, 9.25, 12.95, and 18.5 MBq 131I solution to construct hypothyroidism models and the control group was injected with the same amount of normal saline. The body mass of rats was measured before 131I injection, 4, 8, 12, and 16 weeks after injection of 131I. The serum levels of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, and uric acid were determined by an ELISA kit. Thyroid function was evaluated by 131I static imaging and morphological changes of thyroid tissue were observed by hematoxylin-eosin staining. RESULTS AND CONCLUSION: Compared with the control group, the body mass of the rats in the 9.25, 12.95, and 18.5 MBq groups were significantly decreased at 8, 12, and 16 weeks (P < 0.05). The serum thyroid-stimulating hormone concentration gradually increased in the 9.25, 12.95, and 18.5 MBq groups at 4, 8, 12, and 16 weeks, while the levels of free triiodothyronine and free thyroxine gradually decreased (P < 0.05). The levels of alanine aminotransferase and alkaline phosphatase in the 12.95 and 18.5 MBq groups were significantly higher than those in the control group, while the blood urea nitrogen and creatinine levels in the 18.5 MBq group were significantly higher than those in the control group (P < 0.05). The thyroid glands in each group were clearly visualized before 131I injection, and the target-to-nontarget ratio was not significantly different among groups (P > 0.05). Compared with the control group, the thyroid glands of the 9.25, 12.95, and 18.5 MBq groups were not visualized in the 4th week and the target-to-nontarget ratio was significantly decreased (P < 0.05). The thyroid glands were undeveloped at the 8-, 12-, and 16-week follow-up visits, but there was no statistical difference in the target-to-nontarget ratio among groups (P > 0.05). After injection of 131I, the thyroid follicles of rats became smaller and shrunken, and some of them were irregular. All these findings indicate that intraperitoneal injection of 131I at a dose of 9.25 MBq could successfully establish a stable hypothyroid model in rats within 4 weeks, which provide a reference for the establishment of animal models in the field of nuclear medicine 131I therapy. [ABSTRACT FROM AUTHOR]