Activated Microglia in the Brain: Mitochondrial and Cell Membrane-Associated Targets for Positron Emission Tomography

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 C]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.

Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors

“…Although with focus on the visualization of microglia as an indicator of inflammatory active processes, hitherto, the TSPO ligands continue to be the favored tool in PET imaging [ 92 , 152 ], it can be noted that there are some efforts in identification of targets and small molecule ligands which potentially differentiate between activated and resting microglia. Notably, P2Y12 receptor expression in microglia is a promising interesting target [ 28 ].…”

“…Small molecules have been in series of thio thiazolo pyrimidines (Astra Zeneca) as orally applicable lead structures [ 85 , 86 , 92 ] such as the allosteric, non-competitive CX3CR1 ligand AZD8797( Figure 7 : [ 28 ]) developed for treatment of multiple sclerosis. The first F-18 labeled compound for PET applications was released 2015 with the fluorobenzylthiothiazolopyrimidine FBTTP as a derivative of AZD8797 ( Figure 7 : [ 29 ]) [ 92 , 93 , 94 ].…”