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 [¹⁸F]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 ([¹⁸F]FDG) and [¹⁸F]DPA714. We also studied the BAT uptake of [¹⁸F]DPA714 in CT26, A549 and LLC tumor models. The dynamic distribution of [¹⁸F]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, [¹⁸F]DPA714 produced high-quality and stable BAT imaging in different tumor models and different animals of the same model. Interestingly, %ID/g-mean of [¹⁸F]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 [¹⁸F]DPA714 PET imaging in investigating BAT and energy metabolism during tumor progression in preclinical and clinical study.

KEYWORDS:

• Brown adipose tissue
• [¹⁸F]DPA714
• [¹⁸F]FDG
• PET
• tumour
• energy metabolism

Author contributions

Na Niu and Haiqun Xing participated in the design of the study, data acquisition, statistical analysis, and drafting of manuscript. Xuezhu Wang, Jie Ding, Chao Ren and Zhixin Hao participated in cell culture, radiolabeling and animal experiments. Jiantao Ba, Lianfang Zheng and Chao Fu participated in the imaging data analysis. Li Huo and Haiyan Zhao participated in study design and revised the manuscript. All authors read and approved the final manuscript.

Disclaimer

Funding entities did not contribute to the study design or data collection, analysis and interpretation and the writing of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Volunteer consent

Obtained.

Ethics approval

All experiments were conducted in compliance with the relevant laws and institutional guidelines of Beijing Union Hospital.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was sponsored in part by the National Natural Science Foundation of China (Grant No. 81571713), CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant No. 2016-I2M-4-003), and CAMS initiative fund for innovative medicine (No. CAMS-2018-I2M-3-001).