Repeatability of brown adipose tissue activation measured by [18F]FDG PET after beta3-adrenergic stimuli in a mouse model

Abstract

This study aimed to evaluate the repeatability of brown adipose tissue (BAT) activation measured by [¹⁸F]FDG-PET after beta3-adrenergic stimuli with CL316243 in mice.

Methods: Male C57BL/6 mice underwent [¹⁸F]FDG-PET at baseline without stimulation (T0-NS), on three consecutive days after intravenous administration of the selective β3-adrenergic agonist CL316243 (T1-CL, T2-CL, T3-CL), and without stimuli after 1 and 2 weeks (T7-NS and T14-NS). The standardized uptake value (SUVmax), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were measured in each scanning session, with statistical groupwise comparisons by ANOVA and post hoc Tukey test.

Results: SUVmax, BMV, and TBG values showed no significant differences between the three PET scans without stimuli, but were significantly higher after CL316243 administration (p < 0.0001). The mean coefficient of variation (CoV) of PET within individuals was 49 % at baseline but only 9 % with pharmacological stimulation.

Conclusions: The study demonstrated that administration of the selective β3-adrenergic receptor agonist CL316243 (CL) in mice leads to consistent metabolic activation of brown adipose tissue (BAT), as measured by [¹⁸F]FDG-PET. We also demonstrated metabolic activation by repeated pharmacological challenge, without evidence of hysteresis. Thus, the methods used in the current work should serve for further studies on BAT metabolism in experimental animals, with translational value for clinical research.

Keywords: Brown adipose tissue; Positron emission tomography; [(18)F]FDG; beta3-adrenergic stimuli.