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Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
Published on: July 1, 2021
Quantification of Multi-Organ 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme Levels in a Zucker Fatty Rat Model: A
Jason Bini1, Jordan Strober2, Michael Kapinos1
1Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
Background:
In rodents, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the conversion of inactive 11-dehydrocorticosterone to the active hormone corticosterone. Dysregulation of intracellular glucocorticoid action is implicated in metabolic diseases. Assessing 11β-HSD1 enzyme levels in vivo may be key to understanding obesity pathophysiology.
Objective:
We used a Zucker Fatty (ZF) rat model and [18F]AS2471907 PET imaging to determine appropriate kinetic modeling methods and assess changes in 11β-HSD1 levels due to obesity in the liver, white and brown adipose tissue (WAT/BAT), and brain.
Material And Methods:
To validate [18F]AS2471907 PET in preclinical models, time-activity curves (TACs) were generated and kinetic modeling was performed with image-derived input functions (IDIFs) extracted from multiple locations. Quantitative estimates of radioligand binding were compared with ex vivo 11β-HSD1 protein expression. Validated quantitative PET kinetic modeling methods were then used to assess differences in 11β-HSD1 between lean and obese ZF rats. Metabolic disease status was confirmed with stable isotopes tracer studies of glucose and fatty acid metabolism.
Results:
Obesity is associated with decreased brain 11β-HSD1 levels, measured by [18F]AS2471907 PET, which correlated with measures of glucose and fatty acid metabolism.
Conclusion:
We demonstrate that [18F]AS2471907 PET can provide useful quantification of 11β-HSD1 levels in a rodent model of obesity.
