Imaging of translocator protein upregulation is selective for pro‐inflammatory polarized astrocytes and microglia

Translocator protein (TSPO) expression is increased in activated glia, and has been used as a marker of neuroinflammation in PET imaging. However, the extent to which TSPO upregulation reflects a pro‐ or anti‐inflammatory phenotype remains unclear. Our aim was to determine whether TSPO upregulation in astrocytes and microglia/macrophages is limited to a specific inflammatory phenotype. TSPO upregulation was assessed by flow cytometry in cultured astrocytes, microglia, and macrophages stimulated with lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin‐4 (Il‐4). Subsequently, mice were injected intracerebrally with either a TNF‐inducing adenovirus (AdTNF) or IL‐4. Glial expression of TSPO and pro‐/anti‐inflammatory markers was assessed by immunohistochemistry/fluorescence and flow cytometry. Finally, AdTNF or IL‐4 injected mice underwent PET imaging with injection of the TSPO radioligand 18F‐DPA‐713, followed by ex vivo autoradiography. TSPO expression was significantly increased in pro‐inflammatory microglia/macrophages and astrocytes both in vitro, and in vivo after AdTNF injection (p