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Abstract
Introduction: Currently, the reference method of brown adipose tissue (BAT) imaging is 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET). BAT imaging by [18F]FDG PET requires additional stimulation process, which is inconvenient and hard to be standardized. The translocator protein 18 kDa (TSPO) PET has been found to be effective for visualization of BAT. Herein, we evaluated the feasibility of [18F]fluoromethyl-PBR28-d2 ([18F]fmPBR28-d2), a TSPO PET tracer, for interscapular BAT imaging in comparison with [18F]FDG PET.

Methods: C57BL/6 mice were used for the [18F]fmPBR28-d2 and [18F]FDG PET imaging. [18F]fmPBR28-d2 PET was performed in the thermoneutral condition (n = 5) and after cold exposure (4 °C for 4 h) on the next day using the same mice. [18F]FDG PET was performed in the thermoneutral and cold exposure conditions with the same method with [18F]fmPBR28-d2 PET. Ex vivo biodistribution study of [18F]fmPBR28-d2 was performed in ten C57BL/6 mice (5: thermoneutral, 5: cold exposure). TSPO immunohistochemistry was done in interscapular BAT.

Results: The [18F]fmPBR28-d2 PET images showed prominent interscapular BAT uptakes under both thermoneutral and cold exposure conditions. While, the BAT uptake was significantly higher under the cold exposure condition than the thermoneutral condition (12.83 ± 5.06 vs. 22.50 ± 6.03, P = 0.007). Also, [18F]FDG PET imaging showed higher BAT uptake under the cold exposure condition than thermoneutral condition (8.40 ± 0.63 vs. 21.41 ± 4.03, P = 0.001). The interscapular BAT to background (thigh muscle) ratio was higher in [18F]fmPBR28-d2 PET than [18F]FDG PET under both thermoneutral and cold exposure conditions. Ex vivo biodistribution study using [18F]fmPBR28-d2 also showed higher BAT uptake under cold exposure than the thermoneutral condition (8.86 ± 1.74 vs.16.93 ± 4.74, P = 0.036). Also, IHC demonstrated that TSPO expression was significantly increased in the cold exposure group.

Conclusions: [18F]FmPBR28-d2 PET demonstrated prominent interscapular BAT uptakes regardless of additional stimulation, and showed a higher BAT to background ratio than [18F]FDG PET. Also, we found that [18F]fmPBR28-d2 PET uptake and TSPO expression of BAT increased under cold exposure condition. Further works are warranted to assess the clinical significance of TSPO PET uptake in BAT.

Affiliations

Chiwoo Oh  1 , In Ho Song  2 , Wooseung Lee  1 , Miyeon Jeon  1 , Jinyeong Choi  1 , Seungki Baek  1 , Byung Chul Lee  3 , Sang Eun Kim  4 , Hyung-Jun Im  5
1 Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
2 Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea.
3 Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea; Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Republic of Korea. Electronic address: http://tmtl.snu.ac.kr.
4 Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea; Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
5 Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: iiihjjj@gmail.com.