title: The methodology of TSPO imaging with positron emission tomography.
abstract: The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions. It is therefore a target of interest for molecular strategies aimed at imaging neuroinflammation in vivo. For more than 20 years, positron emission tomography (PET) has allowed the imaging of TSPO density in brain using [(11)C]-(R)-PK11195, a radiolabelled-specific antagonist of the TSPO that has demonstrated microglial activation in a large number pathological cohorts. The significant clinical interest in brain immunity as a primary or comorbid factor in illness has sparked great interest in the TSPO as a biomarker and a surprising number of second generation TSPO radiotracers have been developed aimed at improving the quality of TSPO imaging through novel radioligands with higher affinity. However, such major investment has not yet resulted in the expected improvement in image quality. We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers.
authors.affiliation: Institute of Psychiatry, King's College London, London SE5 8AF, U.K. federico.turkheimer@kcl.ac.uk.
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.affiliation: Information Engineering Dept., University of Padova, Padova 35131, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Rizzo
authors.affiliation: Institute of Clinical Sciences, Imperial College London, London W12 0NN, U.K.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Bloomfield
authors.affiliation: Institute of Psychiatry, King's College London, London SE5 8AF, U.K. MRC Institute of Clinical Sciences, Imperial College London, U.K.
authors.forename: Oliver
authors.initials: O
authors.lastname: Howes
authors.affiliation: University of Bordeaux, CNRS, INCIA, UMR 5287, France.
authors.forename: Paolo
authors.initials: P
authors.lastname: Zanotti-Fregonara
authors.affiliation: Information Engineering Dept., University of Padova, Padova 35131, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoldo
authors.affiliation: Institute of Psychiatry, King's College London, London SE5 8AF, U.K.
authors.forename: Mattia
authors.initials: M
authors.lastname: Veronese
mesh_terms: D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D017628:Microglia / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods*; D018079:Receptors, GABA / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D007546:Isoquinolines; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195
keywords: PK11195; endothelium; genetics; heterogeneity; kinetic modelling; methodology; microglia; neuroinflammation; peripheral benzodiazepine receptor (PBR); peripheral benzodiazepine receptor (PBR)28; plasma free fraction; positron emission tomography; schizophrenia; translocator protein (TSPO)