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Many hyperthyroid cats referred for thyroid imaging and 131I therapy are concurrently or recently receiving antithyroid medications. The effect of the antithyroid drug, methimazole, on thyroid uptake of 99mTcO4 and 123I was evaluated in 8 normal cats. Quantitative analysis was used to determine the normal percent dose uptake of 99mTcO4 and 123I, the change in thyroid: salivary ratios (T:S) of 99mTcO4 over time, and the duration of the methimazole effect on thyroid uptake of 123I. Methimazole was administered to 5 cats for 3 weeks in which a hypothyroid state was obtained; 3 cats served as non-treatment controls. 99mTcO4 and 8 and 24 hour 123I imaging was repeated after 3 weeks of methimazole therapy (time of maximum T4 suppression). Methimazole was then discontinued and 123I images and serum T4 concentrations were repeated at 1, 4, 9, 15, and 24 days post withdrawal. The percent dose uptake of 99mTcO4 increased throughout the acquisition period with maximum uptake occurring 4 hour post injection. The baseline 20 min. T:S ratio for controls and treatment cats were 0.79 ± 0.08 and 0.81 ± 0.05 respectively; with a peak value of 1.29 ± 0.23 and 1.31 ± 0.18 at 4 hours. The baseline T:S ratios were not significantly different from 20 minutes to 2 hours, however they were significantly elevated at 4 hours post injection. Baseline, 8 and 24 hour percent dose uptake of 123I were 2.1 ± 0.42% and 7.04 ± 1.24%, respectively. There was a significant increase in the T:S ratio in the treatment group at all time points. The 8 hour percent dose uptake of 123I at 1, 4, and 9 days post methimazole withdrawal were significantly increased and peaked at 4 days. The 24 hour uptake was significantly increased at 4 and 9 days, with peak uptake at 9 days post-methimazole withdrawal. The 123I percent dose uptake decreased to baseline values by day 15 post withdrawal. Radioiodine uptake is not inhibited by methimazole treatment in normal cats, and is significantly enhanced after recent withdrawal. This finding is supportive of a “short term rebund effect” with maximal enhanced uptake between 4 and 9 days after discontinuing antithyroid drugs. The increased uptake of 99mTcO4 may also affect the interpretation of 99mTcO4 thyroid scintigraphy for 2–3 weeks.