The Translocator Protein

Abstract

The translocator protein (TSPO) is expressed at low levels in the healthy human brain and is markedly upregulated in response to brain injury and inflammation. This increase in TSPO expression is correlated to the extent of microglial activation, making the measurement of TSPO density a useful indicator of active brain disease. Several classes of TSPO radioligands have therefore been developed and evaluated for use in PET, to track the progression and severity of neuroinflammatory disease. TSPO is also overexpressed in cancer and peripheral inflammation, making TSPO PET ligands possible candidates for the imaging of a multitude of pathologies. However, we currently possess a limited understanding about the molecular structure of TSPO and about the interaction of ligands with the protein. Furthermore, the incomplete characterization of multiple TSPO binding sites and the role of TSPO polymerization suggest that current interpretation of PET data may require further refinement.

Metabolism and Quantification of [18F]DPA-714, a New TSPO Positron Emission Tomography Radioligand

“…The 18-kDa translocator protein (TSPO) is a heteropolymeric mitochondrial protein (Scarf, 2011). TSPO is primarily located at outer mitochondrial membranes within transmembrane channels (Lacapère and Papadopoulos, 2003) that have many putative functions (Batarseh and Papadopoulos, 2010;Chelli et al, 2004;Rupprecht et al, 2010).…”

The 18-kDa Mitochondrial Translocator Protein in Human Gliomas: An 11C-(R)PK11195 PET Imaging and Neuropathology Study

“…The 18-kDa mitochondrial translocator protein (TSPO) is a promising candidate for a theranostic approach of gliomas as it can be visualized and quantified with PET and because it is highly expressed in astrocytomas (5,6), but its expression is low in the normal brain. In view of this evidence, experimental studies proposed the TSPO as a target for selective delivery of anticancer drugs into glioma cells or to be exploited as a transporter of drugcontaining nanoparticles (7)(8)(9).…”

Imaging Pulmonary Inflammation

“…The 18-kDa translocator protein, previously known as the peripheral benzodiazepine receptor, is upregulated in activated microglia, a macrophage lineage cell in the brain (35). The radiolabeled isoquinoline 11 C-PK11195 binds specifically to translocator protein, and its binding correlates with macrophage recruitment in rabbit lungs after silica particle challenge (36).…”