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 [11C]-(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.
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August 2015
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Review Article|
August 03 2015
The methodology of TSPO imaging with positron emission tomography
Federico E. Turkheimer;
Federico E. Turkheimer
1
*Institute of Psychiatry, King's College London, London SE5 8AF, U.K.
1To whom correspondence should be addressed (email federico.turkheimer@kcl.ac.uk).
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Gaia Rizzo;
Gaia Rizzo
†Information Engineering Dept., University of Padova, Padova 35131, Italy
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Peter S. Bloomfield;
Peter S. Bloomfield
‡Institute of Clinical Sciences, Imperial College London, London W12 0NN, U.K.
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Oliver Howes;
Oliver Howes
*Institute of Psychiatry, King's College London, London SE5 8AF, U.K.
§MRC Institute of Clinical Sciences, Imperial College London, U.K.
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Paolo Zanotti-Fregonara;
Paolo Zanotti-Fregonara
║University of Bordeaux, CNRS, INCIA, UMR 5287, France
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Alessandra Bertoldo;
Alessandra Bertoldo
†Information Engineering Dept., University of Padova, Padova 35131, Italy
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Mattia Veronese
Mattia Veronese
*Institute of Psychiatry, King's College London, London SE5 8AF, U.K.
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Biochem Soc Trans (2015) 43 (4): 586–592.
Article history
Received:
February 25 2015
Citation
Federico E. Turkheimer, Gaia Rizzo, Peter S. Bloomfield, Oliver Howes, Paolo Zanotti-Fregonara, Alessandra Bertoldo, Mattia Veronese; The methodology of TSPO imaging with positron emission tomography. Biochem Soc Trans 1 August 2015; 43 (4): 586–592. doi: https://doi.org/10.1042/BST20150058
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