TITLE:
Activated Microglia in the Brain: Mitochondrial and Cell Membrane-Associated Targets for Positron Emission Tomography
AUTHORS:
Margit Pissarek
KEYWORDS:
Microglia, Inflammation, Brain, PET, TSPO, CX3CR1, Folate Receptor
JOURNAL NAME:
World Journal of Neuroscience,
Vol.8 No.1,
January
31,
2018
ABSTRACT: The emission tomographic imaging of activated
microglia in the brain moves into the focus of neuroscientific research with
increasing recognition of contributions of early inflammatory processes to
neurodegenerative, traumatic, cancerous and infectious diseases of the brain.
Whereas the mitochondrial isoform of the 18 kDa translocator protein (TSPO1)
has been the main cellular target for positron emission tomography (PET) of
this type of cells for decades, alternative marker proteins in the plasma
membrane of microglia challenge efforts in ligand development, recently. The
present report includes PET approaches using the chemokine receptor CX3CR1 and
the FR2 folate receptor in parallel to small molecule PET tracers available for in vivo visualization of the
“classical” target TSPO1. It compares first and second generation of TSPO1 ligands as well as new compounds like the
tetrahydrocarbazole [18F]GE-180 and the quinazoline [11C]ER176
presumed to reduce polymorphism-related inter-subject variations, with
allosteric ligands for the chemokine receptor CX3CR1 and with radio labelled
folate conjugates targeting the folate “cargo” receptor FR1 and the FR2
receptor characteristic for anti-inflammatory M2 microglia.