PET imaging of brown adipose tissue using fluorine 18-labeled TSPO ligand DPA-714

Objectives: Brown adipose tissue (BAT) plays a key role in regulation of body temperature in mammals including humans through uncoupled protein-1 (UCP-1) located in mitochondria. Fluorine-18 labeled FDG PET imaging has been wildly used to evaluate BAT function and its potential anti-obesity property in adults for several decades. However, [¹⁸F]FDG does not directly reflect the mitochondrial activity of BAT, which may lead to misestimating its metabolic activity. Translocator protein (TSPO) is expressed on mitochondria membrane of different tissues including BAT and participates in many mitochondrial functions. Therefore, the aim of our study was to evaluate the utility of [¹⁸F] DPA-714, a ligand of TSPO, in BAT metabolic activity. And we hypothesized that the metabolic change of BAT under different conditions could be monitored by TSPO PET imaging.

Methods: TSPO expression in BAT was confirmed by ex vivo immunohistological staining of BAT slices. Automated syntheses of [¹⁸F]DPA-714 were carried out using a slightly modified TRACERLab FX-FN module (GE Medical Systems, Germany). The specificity of [¹⁸F]DPA-714 uptake in BAT was confirmed by a displacement study with unlabeled DPA-714. TSPO PET imaging was performed in 3 groups of Balb/c mice using a small animal PET scanner (Inveon, Siemens)(non-treated group: n=3, cold treated group: n=3, and CL 316-243 treated group: n=3, respectively). All mice were euthanized for DPA-714 bio-distribution assay after in vivo study.

Results: Immunohistological staining confirmed the diffused expression of TSPO in BAT. In vivo PET imaging revealed that [¹⁸F]DPA-714 uptake was in a butterfly shape at the interscapular BAT of non-treated mice. And the specific uptake was proved by a dramatic signal loss after cold DPA-714 replacement. The signal intensity of [¹⁸F]DPA-714 significantly increased by 2 to 3 times in both CL 316,243 and cold treated groups. Ex vivo bio-distribution assay confirmed the intensively increased [¹⁸F]DPA-714 uptake in CL 316,243 and cold activated BAT.

Conclusion: TSPO-targeted PET imaging using [¹⁸F]DPA-714 as a probe could be used to noninvasively monitor BAT activation. And this would not only provide an additional new method for in vivo BAT imaging, but also facilitate further investigation of mitochondrial function in activated BAT. Research Support: Supported by National Natural Science Foundation of China (Grant No: 81501507)