Abstract 222: Translocator Protein as Novel Marker for Early Atherosclerosis

Atherosclerosis is characterized by lipid deposition, monocyte infiltration and foam cell formation in the artery wall. Translocator protein (TSPO) is abundantly expressed in lipid rich tissues. Recently, TSPO has been identified as a potential diagnostic tool in cardiovascular disease. Here, we aimed to determine if (i) the TSPO radioligand, 18 F-PBR111, can identify fatty streak formation that precedes atherosclerotic lesion development and (ii) TSPO expression can be used to identify distinct macrophage populations during different stages of lesion progression. Atherosclerosis-prone apoE -/- mice were maintained on a high-fat diet for 3, 9 and 12 weeks. C57BL6 mice maintained on chow diet served as controls. Mice were anesthetized, injected with 18 F-PBR111 (8-18 MBq, 0.1 mL, 0.2 nM) via the lateral tail vein and imaged using an Inveon PET/CT Scanner over 60 min. After euthanasia, aortas were isolated, fixed and optically cleared. Cleared aortas were immunostained with DAPI, fluorescently labelled anti-TSPO antibody and the macrophage markers F4/80 and CD11b. Tissues were visualized on a Lightsheet Z.1 microscope and analysed with 3D imaging software. A 3-fold increase in the uptake of 18 F-PBR111 was observed by PET/CT in the aortas of atherosclerotic mice relative to controls. Increased 18 F-PBR111 uptake was observed in the aortic arch and thoracic aorta, corresponding with sites of atherosclerotic lesion development. Light sheet microscopy revealed that TSPO expression increased correspondingly to atherosclerosis progression. The expression pattern of macrophage populations in early lesions differed from that in mature plaques. While F4/80-positive macrophages were evident uniformly throughout the aortas, CD11b-positive macrophages were increased in atherosclerotic areas. In conclusion, imaging TSPO expression is a new approach for studying atherosclerotic lesion progression and is associated with specific inflammatory cell infiltration. The TSPO ligand 18 F-PBR111 is a potential clinical diagnostic tool for the detection and quantification of atherosclerotic lesion progression in humans.