Effect of clod exposure on TSPO targeting PET tracer uptake in brown adipose tissue

415 Objectives: The current approach for brown adipose tissue (BAT) imaging is utilizing 18F-Fluorodeoxyglucose positron emission tomography (FDG PET). A primary weakness of BAT imaging by FDG PET is the need for additional stimulation such as cold exposure. BAT is characterized by the abundance of mitochondria which has a high expression of translocator protein (TSPO). Herein, we tested the feasibility of TSPO PET for BAT imaging and evaluated BAT uptakes and TSPO expression in thermoneutral and cold exposure conditions. Methods: Five c57/bl6 mice were used for the TSPO PET imaging. 18F-PBR28, a TSPO PET tracer, was injected into the mice intravenously (400 μCi/mouse). The mice were kept in the thermoneutral condition for thirty minutes after the injection, and the PET images were acquired for 20 minutes. The next day, TSPO PET imaging was performed again using the same five mice after cold exposure (4℃ for 4 hours, cold exposure condition). Ex vivo biodistribution study was performed in ten c57/bl6 mice (5: thermoneutral, 5: cold exposure). 30 minutes after injection of 18F-PBR28 (200 μCi/mouse), the mice were sacrificed, and the organs were collected for the gamma counting and immunohistochemistry (IHC). The values of two groups was compared by paired t-test or independent samples t-test. Immunohistochemistry (IHC) was performed using anti TSPO antibody and the images were obtained using a confocal microscopy. Results: The TSPO PET images showed prominent BAT uptakes in both thermoneutral and cold exposure conditions. However, the BAT uptake was significantly higher at the cold exposure condition than the thermoneutral condition (paired t-test, P = 0.02) (Fig. A). Ex vivo biodistribution study corroborated with the finding of PET study. The %ID/g of blood, kidney, and BAT were significantly higher in the cold exposure group than those in thermoneutral group (blood: 0.97±0.10 vs. 1.48±0.14, P = 0.0001, kidney: 18.24 vs. 24.56, P = 0.009, and BAT: 20.49 vs. 39.87, P = 0.025). However, the uptakes of lung and muscle were not significantly different between the two groups (lung: 12.47 vs. 14.26, P = 0.344, muscle: 3.81 vs. 4.95, P = 0.24) (Fig. B). Also, confocal microscopy images demonstrated that TSPO expression was notably increased in cold exposure group (Fig. C). Conclusions: TSPO PET could demonstrate prominent BAT uptake regardless of additional stimulation. Also, we found that TSPO 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 and underlying biological process regarding the association between TSPO expression and thermogenesis in BAT during cold exposure.