Preclinical [¹⁸F]FDG PET/MR: The influence of thyroid dysfunction on the activity of brown adipose tissue (BAT) in mice

Thyroid hormones (TH) are crucial regulators of energy metabolism. This is in particular exemplified in patients with thyroid dysfunction disorders leading to hyperthyroidism or hypothyroidism (Brent et al. 2012). Hyperthyroidism, which is associated with excessive levels of TH, leads to an increased metabolic rate and weight loss despite increased food intake. In contrast, hypothyroid patients exhibit a decreased metabolic rate and gain weight despite reduced food intake (Lopez et al. 2010). These effects have been attributed on direct actions of TH on metabolically active tissues, such as brown adipose tissue (BAT) (Bianco et al. 2005). In this study we aimed to evaluate the impact of hyper- and hypothyroidism on BAT activity of C57BL/6 mice using [¹⁸F]FDG PET/MRI. To generate hyperthyroidism, mice received L-thyroxine daily (2 µg/ml diluted in drinking water). Hypothyroidism was generated by application of an iodine deficient diet containing 0.15% propylthiouracil (TD.95125, Harlan Laboratories). After 4 weeks of treatment n=4 mice per group (23.7 g±1.2 g body weight) were injected i.p. with [¹⁸F]FDG (14.5±1.3 MBq). Thirty minutes post injection the mice were imaged in a small animal PET/MR device (nanoscan®, Mediso, Hungary) up to 30 min. Followed by a whole-body MR scan (gradient echo sequence, TR=20 ms, TE= 3.2 ms) for anatomical orientation and attenuation correction. Metabolic activity of BAT was determined by quantification of the glucose uptake (SUVmean) in typical regions of BAT (supraclavicular neck) using MR-based VOI analysis (PMOD v. 3.3).
The comparison of SUVmean (Figure 1) of the hyperthyroid mice showed a significantly increased [¹⁸F]FDG uptake compared to the control group (SUVmean 8.78 ± 2.08 and 6.16 ± 0.57, respectively; p = 0.05). However, in hypothyroid mice, a reduced FDG uptake was observed (SUVmean = 3.53 ± 0.65; p<0.01 vs. hyperthyroid and vs. control, respectively).
In conclusion, these findings substantiate the use of [¹⁸F]FDG PET/MRI as a valuable tool to map the effects of thyroid hormones on BAT activity. Furthermore, this is the first study confirming decreased supraclavicular BAT activation in hypothyroid mice.

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