Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea.
Nucl Med Biol. 2020 Nov-Dec;90-91:98-103. doi: 10.1016/j.nucmedbio.2020.10.001. Epub 2020 Oct 26.
Currently, the reference method of brown adipose tissue (BAT) imaging is F-fluorodeoxyglucose positron emission tomography ([F]FDG PET). BAT imaging by [F]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 [F]fluoromethyl-PBR28-d ([F]fmPBR28-d), a TSPO PET tracer, for interscapular BAT imaging in comparison with [F]FDG PET.
C57BL/6 mice were used for the [F]fmPBR28-d and [F]FDG PET imaging. [F]fmPBR28-d 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. [F]FDG PET was performed in the thermoneutral and cold exposure conditions with the same method with [F]fmPBR28-d PET. Ex vivo biodistribution study of [F]fmPBR28-d was performed in ten C57BL/6 mice (5: thermoneutral, 5: cold exposure). TSPO immunohistochemistry was done in interscapular BAT.
The [F]fmPBR28-d 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, [F]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 [F]fmPBR28-d PET than [F]FDG PET under both thermoneutral and cold exposure conditions. Ex vivo biodistribution study using [F]fmPBR28-d 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.
[F]FmPBR28-d PET demonstrated prominent interscapular BAT uptakes regardless of additional stimulation, and showed a higher BAT to background ratio than [F]FDG PET. Also, we found that [F]fmPBR28-d 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.
目前，棕色脂肪组织（BAT）成像的参考方法是 F-氟脱氧葡萄糖正电子发射断层扫描（[F]FDG PET）。[F]FDG PET 进行 BAT 成像需要额外的刺激过程，既不方便也难以标准化。转位蛋白 18 kDa（TSPO）PET 已被发现可有效可视化 BAT。在此，我们评估了 TSPO PET 示踪剂[F]氟甲基-PBR28-d（[F]fmPBR28-d）用于肩胛间 BAT 成像的可行性，与[F]FDG PET 进行了比较。
使用 C57BL/6 小鼠进行[F]fmPBR28-d 和[F]FDG PET 成像。[F]fmPBR28-d PET 在常温（n=5）和次日冷暴露（4°C 4 小时）下进行。[F]FDG PET 以与[F]fmPBR28-d PET 相同的方法在常温和冷暴露条件下进行。在 10 只 C57BL/6 小鼠（5 只：常温，5 只：冷暴露）中进行了[F]fmPBR28-d 的离体生物分布研究。在肩胛间 BAT 中进行了 TSPO 免疫组织化学染色。
[F]fmPBR28-d PET 图像在常温和冷暴露条件下均显示出明显的肩胛间 BAT 摄取。然而，冷暴露条件下的 BAT 摄取明显高于常温条件（12.83±5.06 比 22.50±6.03，P=0.007）。此外，[F]FDG PET 成像显示冷暴露条件下的 BAT 摄取高于常温条件（8.40±0.63 比 21.41±4.03，P=0.001）。在常温和冷暴露条件下，[F]fmPBR28-d PET 肩胛间 BAT 与背景（大腿肌肉）的比值均高于[F]FDG PET。使用[F]fmPBR28-d 的离体生物分布研究也显示，冷暴露条件下的 BAT 摄取高于常温条件（8.86±1.74 比 16.93±4.74，P=0.036）。免疫组化也表明，TSPO 表达在冷暴露组中明显增加。
[F]fmPBR28-d PET 显示出明显的肩胛间 BAT 摄取，无需额外的刺激，与[F]FDG PET 相比，BAT 与背景的比值更高。此外，我们发现冷暴露条件下[F]fmPBR28-d PET 摄取和 BAT 中 TSPO 的表达增加。需要进一步的工作来评估 BAT 中 TSPO PET 摄取的临床意义。
