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Imaging Adipose Tissue Browning using Mitochondrial Complex-I Tracer [18F]BCPP-EF.

Julian L Goggi1, Siddesh Hartimath1, Shivashankar Khanapur1

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|June 13, 2022
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Summary

A new tracer, [18F]BCPP-EF, can detect newly formed beige adipocytes in white adipose tissue earlier and more effectively than [18F]FDG. This mitochondrial complex-I marker shows promise for evaluating obesity and metabolic disease therapies.

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Area of Science:

  • Metabolic research
  • Adipose tissue biology
  • Medical imaging

Background:

  • Browning of white adipose tissue (WAT) into beige adipocytes is a potential strategy against obesity.
  • Noninvasive methods to quantify beige adipocytes in WAT are lacking.
  • Current imaging with [18F]FDG has unclear relationships with beige adipocyte function and thermogenesis.

Purpose of the Study:

  • To evaluate [18F]BCPP-EF, a tracer for mitochondrial complex-I (MC-I), as a marker for newly formed beige adipocytes.
  • To compare the efficacy of [18F]BCPP-EF with [18F]FDG in detecting thermogenic changes in WAT.

Main Methods:

  • Mice were treated with the β3-adrenergic agonist CL-316,243 for 7 days to induce beige adipocyte formation in inguinal WAT.
  • Longitudinal PET imaging was performed using both [18F]FDG (glycolysis marker) and [18F]BCPP-EF (MC-I marker).
  • The effect of adrenoceptor antagonist on [18F]BCPP-EF uptake was assessed.

Main Results:

  • CL-316,243 treatment significantly increased both [18F]FDG and [18F]BCPP-EF uptake in inguinal WAT.
  • [18F]BCPP-EF uptake increased significantly after 3 days, while [18F]FDG showed significant increase only after 7 days.
  • [18F]BCPP-EF uptake in newly formed beige adipocytes was blocked by an adrenoceptor antagonist, unlike in BAT.

Conclusions:

  • [18F]BCPP-EF can detect newly formed beige adipocytes in WAT induced by β3-adrenergic stimulation.
  • This MC-I tracer demonstrates earlier detection and higher uptake in inguinal WAT compared to [18F]FDG.
  • [18F]BCPP-EF is a promising tool for evaluating therapeutic strategies targeting metabolic adipose tissues for obesity and related diseases.