A Novel PET Probe for Brown Adipose Tissue Imaging in Rodents

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.

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.

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.

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.