Brown adipose tissue imaging using the TSPO tracer [18F]fluoromethyl-PBR28-d2: A comparison with [18F]FDG

Nucl Med Biol. 2020 Nov-Dec:90-91:98-103. doi: 10.1016/j.nucmedbio.2020.10.001. Epub 2020 Oct 26.

Abstract

Introduction: Currently, the reference method of brown adipose tissue (BAT) imaging is 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET). BAT imaging by [18F]FDG PET requires additional stimulation process, which is inconvenient and hard to be standardized. The translocator protein 18 kDa (TSPO) PET has been found to be effective for visualization of BAT. Herein, we evaluated the feasibility of [18F]fluoromethyl-PBR28-d2 ([18F]fmPBR28-d2), a TSPO PET tracer, for interscapular BAT imaging in comparison with [18F]FDG PET.

Methods: C57BL/6 mice were used for the [18F]fmPBR28-d2 and [18F]FDG PET imaging. [18F]fmPBR28-d2 PET was performed in the thermoneutral condition (n = 5) and after cold exposure (4 °C for 4 h) on the next day using the same mice. [18F]FDG PET was performed in the thermoneutral and cold exposure conditions with the same method with [18F]fmPBR28-d2 PET. Ex vivo biodistribution study of [18F]fmPBR28-d2 was performed in ten C57BL/6 mice (5: thermoneutral, 5: cold exposure). TSPO immunohistochemistry was done in interscapular BAT.

Results: The [18F]fmPBR28-d2 PET images showed prominent interscapular BAT uptakes under both thermoneutral and cold exposure conditions. While, the BAT uptake was significantly higher under the cold exposure condition than the thermoneutral condition (12.83 ± 5.06 vs. 22.50 ± 6.03, P = 0.007). Also, [18F]FDG PET imaging showed higher BAT uptake under the cold exposure condition than thermoneutral condition (8.40 ± 0.63 vs. 21.41 ± 4.03, P = 0.001). The interscapular BAT to background (thigh muscle) ratio was higher in [18F]fmPBR28-d2 PET than [18F]FDG PET under both thermoneutral and cold exposure conditions. Ex vivo biodistribution study using [18F]fmPBR28-d2 also showed higher BAT uptake under cold exposure than the thermoneutral condition (8.86 ± 1.74 vs.16.93 ± 4.74, P = 0.036). Also, IHC demonstrated that TSPO expression was significantly increased in the cold exposure group.

Conclusions: [18F]FmPBR28-d2 PET demonstrated prominent interscapular BAT uptakes regardless of additional stimulation, and showed a higher BAT to background ratio than [18F]FDG PET. Also, we found that [18F]fmPBR28-d2 PET uptake and TSPO expression of BAT increased under cold exposure condition. Further works are warranted to assess the clinical significance of TSPO PET uptake in BAT.

Keywords: Brown adipose tissue; Positron emission tomography; Translocator protein.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemistry*
  • Acetamides / pharmacokinetics
  • Adipose Tissue, Brown / diagnostic imaging*
  • Aminopyridines / chemistry*
  • Aminopyridines / pharmacokinetics
  • Animals
  • Fluorodeoxyglucose F18*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Positron-Emission Tomography / methods*
  • Radioactive Tracers
  • Receptors, GABA / metabolism*
  • Tissue Distribution

Substances

  • Acetamides
  • Aminopyridines
  • Bzrp protein, mouse
  • N-(6-fluoro-4-phenoxypyridin-3-yl)-N-(2-methoxybenzyl)acetamide
  • Radioactive Tracers
  • Receptors, GABA
  • Fluorodeoxyglucose F18