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A Novel PET Probe for Brown Adipose Tissue Imaging in Rodents

  • Hui Wang
  • Mengzhe Wang
  • Kantapat Chansaenpak
  • Yang Liu
  • Hong Yuan
  • Jin Xie
  • Hang Yin
  • Rosa T. Branca
  • Zibo Li
  • Zhanhong WuEmail author
Research Article

Abstract

Purpose

Brown adipose tissue (BAT) has emerged as a promising target to counteract obesity and its associated metabolic disorders. However, the detection of this tissue remains one of the major roadblocks.

Procedures

In this study, we assess the use of BODIPY 1 as a positron emission tomography (PET) imaging agent to image BAT depots in vivo in two mouse phenotypes: obesity-resistant BALB/c mice and the obesity-prone C57BL/6 mice. [18F]BODIPY 1 is a radioactive dye that processed both radioactivity for PET imaging and fluorescence signal for in vitro mechanism study.

Results

Through the co-staining of cancer cells with BODIPY 1 and MitoTracker, we found BODIPY 1 mainly accumulated in cell mitochondria in vitro. Fluorescence imaging of primary brown and white adipocytes further confirmed BODIPY 1 had significantly higher accumulation in primary brown adipocytes compared with primary white adipocytes. We evaluated [18F]BODIPY 1 for BAT imaging in both obesity-resistant BALB/c mice and obesity-prone C57BL/6 mice. Indeed, [18F]BODIPY 1 was efficiently taken up by BAT in both mouse genotypes (6.40 ± 1.98 %ID/g in obesity-resistant BALB/c mice (n = 8) and 5.37 ± 0.82 %ID/g in obesity-prone C57BL/6 mice (n = 7)). Although norepinephrine stimulation could increase the absolute BAT uptake, the enhancement is not significant in both genotypes (p > 0.05) at current sample size. These results suggest BAT uptake of [18F]BODIPY 1 may be independent of BAT thermogenic activity. As a comparison, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET imaging was performed in obesity-resistant BALB/c mice. Significantly increased uptake was observed in adrenergically activated BAT (10.08 ± 2.52 %ID/g, n = 3) but not in inactive BAT (3.803 ± 0.70 %ID/g; n = 3). Because [18F]BODIPY 1 maintained its fluorescent property, BAT tissue was excised and studied using fluorescence microscopy. Strong fluorescence signal was observed in BAT mouse that was injected with BODIPY 1.

Conclusions

Unlike [18F]FDG, [18F]BODIPY 1 showed prominent accumulation in BAT under both inactive and stimulated status. [18F]BODIPY 1 may serve as a valuable BAT PET agent to possibly assess BAT mitochondria density, thus BAT thermogenic capacity after further evaluation.

Key words

Brown adipose tissue BODIPY Positron emission tomography Thermogenesis 

Notes

Funding Information

This study was supported by Start-Up grant from the Department of Radiology, University of North Carolina at Chapel Hill (Z.W.) and R01DK108231 (R.T.B.).

Compliance with Ethical Standards

Animal procedures were performed according to a protocol approved by the Institutional Animal Care and Use Committee (IACUC) of the University of North Carolina.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© World Molecular Imaging Society 2019

Authors and Affiliations

  1. 1.Department of Radiology and Biomedical Research Imaging CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Center for Molecular Medicine, Department of Biochemistry and Molecular BiologyThe University of GeorgiaAthensUSA
  3. 3.Biomedical Research Imaging CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  4. 4.Department of Chemistry, Bio-Imaging Research CenterThe University of GeorgiaAthensUSA
  5. 5.Department of Physics and AstronomyUniversity of North Carolina at Chapel HillChapel HillUSA

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