Translocator Protein Imaging in Neurological Disorders

Translocator protein (TSPO) imaging has become a pivotal tool for the non-invasive assessment of neuroinflammation across a range of neurological disorders. TSPO, an 18 kDa mitochondrial outer-membrane protein, is upregulated in activated glial cells and other CNS cell types in response to injury or disease. By utilising positron emission tomography (PET) with selective radioligands, researchers can visualise and quantify regional neuroinflammatory changes in vivo, monitor disease progression and evaluate therapeutic modulation. Advances in tracer chemistry, kinetic modelling and molecular biology have refined the specificity of TSPO ligands, addressed genetic polymorphism effects on binding affinity and improved the translational fidelity from preclinical models to human studies. Consequently, TSPO imaging has informed our understanding of Alzheimer’s disease, multiple sclerosis, prion disorders and other neurodegenerative conditions, offering insights into cellular contributors to pathology and the efficacy of anti-inflammatory interventions.

Research from Nature Portfolio

Functional knockout models lacking TSPO have provided seminal evidence on ligand specificity and the biological role of the protein. In particular, studies employing global TSPO-deficient mice demonstrated that canonical ligands such as PK11195, CLINDE and PBR111 lose their in vivo binding in the absence of the target, confirming TSPO as the exclusive molecular substrate for these radiotracers. Surprisingly, despite earlier assumptions, TSPO deletion did not impair cholesterol transport or steroidogenesis to the degree anticipated, although microglial metabolic activity was attenuated. These findings have established a robust platform for validating new PET ligands, clarifying the mechanism of action of TSPO-targeting drugs and guiding interpretation of imaging data in health and disease.

Translocator Protein Imaging in Neurological Disorders publication trend

The graph below shows the total number of articles in translocator protein imaging in neurological disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Translocator protein (TSPO): An 18 kDa mitochondrial outer-membrane protein upregulated in activated glia and other CNS cells, serving as a biomarker of neuroinflammation.

Positron emission tomography (PET): A nuclear imaging technique that uses radiolabelled compounds to visualise and quantify molecular targets in vivo.

Radioligand: A radioactively labelled molecule designed to bind selectively to a specific protein or receptor for imaging or autoradiography.

Neuroinflammation: The inflammatory response within the central nervous system, characterised by activation of microglia, astrocytes and recruitment of peripheral immune cells.

Volume of distribution (VT): A kinetic parameter reflecting the equilibrium ratio of radioligand concentration in tissue relative to plasma, used to quantify receptor or protein binding in PET studies.

Standardised uptake value (SUV): A semiquantitative PET metric representing tissue tracer concentration normalised by injected dose and body weight.

References

1. Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease. Journal of Neuroinflammation (2023).
2. Quantitative assessment of translocator protein (TSPO) in the non-human primate brain and clinical translation of [18F]LW223 as a TSPO-targeted PET radioligand. Pharmacological Research (2023).
3. Positron emission tomography and functional characterization of a complete PBR/TSPO knockout. Nature Communications (2014).
4. Cellular sources of TSPO expression in healthy and diseased brain. European Journal of Nuclear Medicine and Molecular Imaging (2021).