Comparative [18F]FDG and [18F]DPA714 PET imaging and time-dependent changes of brown adipose tissue in tumor-bearing mice

Abstract

Brown adipose tissue (BAT) is important in monitoring energy homeostasis and cancer cachexia. Different from white adipose tissue, BAT is characterized by the presence of a large number of mitochondria in adipocytes. Translocator protein 18 kDa (TSPO), a critical transporter, is expressed in the outer membrane of mitochondria. We speculated that [ 18 F]DPA714, a specific TSPO tracer, may monitor BAT activity in tumor-bearing mice in vivo. We first analyzed the radioactive uptake of positron emission tomography (PET) tracers in BAT of CT26 xenograft mice with 18F-fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]DPA714. We also studied the BAT uptake of [ 18 F]DPA714 in CT26, A549 and LLC tumor models. The dynamic distribution of [ 18 F]FDG is quite variable among animals, even in mice of the same tumor model (%ID/g-mean: mean ± SDM, 8.61 ± 8.90, n = 16). Contrarily, [ 18 F]DPA714 produced high-quality and stable BAT imaging in different tumor models and different animals of the same model. Interestingly, %ID/g-mean of [ 18 F]DPA714 in BAT was significantly higher on day 26 than that on day 7 in CT26 xenograft model. Taken together, these results strongly indicate the potential feasibility of [ 18 F]DPA714 PET imaging in investigating BAT and energy metabolism during tumor progression in preclinical and clinical study.

Molecular Imaging of Brown Adipose Tissue Mass

“…Notably, there was no significant difference between cold treatment and those under thermo-neutral conditions, indicating that 18 F-F-DPA could serve as a reliable tracer for BAT mass imaging regardless of its activation (Figure 2). To study the relationship of BAT and cancer cachexia, Huo et al compared the 18 F-FDG and 18 F-F-DPA PET imaging of BAT with tumor-bearing mice [59]. Their data showed 18 F-F-DPA have significant uptake in BAT without any stimulation, which was consistent with our previous report [58,62].…”

A hemicyanine-based near-infrared fluorescent probe with large Stokes shift for non-invasive bioimaging of brown adipose tissue

“…8 18 F-FDG-PET was first reported to visualize BAT under pretreatment activation and has become the gold standard for the quantitative assessment of BAT in humans. 9 Subsequently, other PET probes labeled with radionuclides such as F-18, 10–17 C-11, 18,19 or Cu-64 20 have been continually developed to enable specific evaluation of BAT and related biomarkers. Besides, magnetic resonance imaging (MRI) represents another attractive imaging approach to visualize the presence and function of BAT 21 by utilizing various techniques including fat fraction mapping, 22 T 2 *-weighted mapping, 23 blood oxygen level dependent (BOLD) MRI, 24 and hyperpolarized Xenon MRI.…”