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Int. J. Mol. Sci. 2017, 18(4), 802; doi:10.3390/ijms18040802

Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations

1
INSERM U930, Université François Rabelais de Tours, 10 boulevard Tonnelé, 37032 Tours, France
2
CHRU de Tours, 37044 Tours, France
*
Author to whom correspondence should be addressed.
Academic Editors: Styliani-Anna E. Tsirka and Jillian Nissen
Received: 31 January 2017 / Revised: 15 March 2017 / Accepted: 28 March 2017 / Published: 11 April 2017
(This article belongs to the Special Issue Microglia in Aging and Neurodegenerative Disease)
View Full-Text   |   Download PDF [308 KB, uploaded 12 April 2017]

Abstract

Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals’ binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors (purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β) and enzymes (cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway), with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians’ expectations. View Full-Text
Keywords: microglial activation; neuroinflammation; PET; biomarker; neurodegenerative disorders microglial activation; neuroinflammation; PET; biomarker; neurodegenerative disorders
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Tronel, C.; Largeau, B.; Santiago Ribeiro, M.J.; Guilloteau, D.; Dupont, A.-C.; Arlicot, N. Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations. Int. J. Mol. Sci. 2017, 18, 802.

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