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Multimodal functional imaging of brown adipose tissue

Open AccessPublished:November 27, 2020DOI:https://doi.org/10.1194/jlr.ILR120001204
      Brown adipose tissue (BAT) is a mitochondrial dense tissue capable of regulating body temperature and energy balance (
      • Townsend K.
      • Tseng Y.-H.
      Brown adipose tissue.
      ). BAT is a potential therapeutic target for metabolic diseases including obesity and type 2 diabetes (
      • Townsend K.
      • Tseng Y.-H.
      Brown adipose tissue.
      ). Determining in vivo BAT metabolic activity is a powerful tool in translational research. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is the standard technique for imaging BAT glucose uptake as a proxy for thermogenic activity (
      • Borga M.
      • Virtanen K.A.
      • Romu T.
      • Leinhard O.D.
      • Persson A.
      • Nuutila P.
      • Enerbäck S.
      Brown adipose tissue in humans: detection and functional analysis using PET (positron emission tomography), MRI (magnetic resonance imaging), and DECT (dual energy computed tomography).
      ). However, PET is limited by the requirement for radioisotope tracers, associated costs, and a lack of functionality to detect concurrent metabolic processes within the same animal. Multimodal imaging can overcome these limitations. We combined FDG PET with fluorescence optical imaging, a promising technique, not yet widely used in BAT studies (
      • Rice D.R.
      • White A.G.
      • Leevy W.M.
      • Smith B.D.
      Fluorescence imaging of interscapular brown adipose tissue in living mice.
      ). We induced BAT activity in C57BL6 mice with CL316,243, a highly specific beta 3-adrenoreceptor agonist, with 1 mg/kg subcutaneous injection for 3 days. We intravenously injected a commercially available fluorescent probe, RediJect 2-DG (100 μl), 3 h before imaging with an Xtreme II optical imaging system (Bruker, Ettlingen) in CL316,243-treated BAT-activated animals or saline-injected controls (panel A). Anatomical regions of interest were used in analysis of fluorescence optical imaging. Animals treated with beta 3-adrenoreceptor agonist had higher uptake of RediJect 2-DG in BAT, which we confirmed with ex vivo optical imaging of harvested tissues including BAT, subcutaneous white adipose tissue (WAT), and soleus muscle (panel B). Next, we compared RediJect 2-DG to FDG to determine if RediJect 2-DG was a suitable alternative to FDG and to establish the impact of co-injection. We co-injected RediJect 2-DG and FDG into a mouse with induced BAT activity. In succession, we imaged the same mouse with PET/computed tomography to detect the FDG (panel C) and then used optical imaging to detect the RediJect 2-DG (panel D). RediJect 2-DG optical imaging identifies increased activity in the BAT anatomical region as was observed with PET and validated ex vivo using optical imaging and gamma-counter biodistribution analysis. This study is an important step to progress onto wider multitracer work. Simultaneous co-injection of a radioisotope and fluorescent probe could expand current BAT in vivo imaging modalities and facilitate the future detection of multiple concurrent metabolic processes in a single animal.
      EQUIPMENT: Albira Si PET/SPECT/CT (Bruker), Xtreme II optical imaging system (Bruker)
      REAGENTS: XenoLight RediJect 2-DeoxyGlucosone (DG) (PerkinElmer), CL316,243 (Sigma)

      Author ORCIDs

      Funding and additional support

      This work was supported by grants from the Medical Research Council (MR/R014086/1) and the British Heart Foundation .

      Conflict of interest

      The authors declare that they have no conflicts of interest with the contents of this article.

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