Table 2.
Examples of potential alternative molecular targets for radioligands to facilitate CNS PET imaging of microglial activation. Both current and proposed molecular targets are outlined
| Molecular target | Cellular localisation | Cell type expression | Function | M1/M2 differentiation | Current application or proposed |
|---|---|---|---|---|---|
| COX | Cytoplasmic enzyme | Microglia, neurones | Synthesis of prostaglandins | No data yet available | Current—murine models |
| P2X7R | Cation-permeable ion channel receptor | Microglia, astrocytes, macrophages, Schwann cells | Activates proinflammatory cytokines (IL-1β) and ROS release | Potentially is specific for the M1 phenotype | Current—murine model |
| CB2R | G protein-coupled receptor | Microglia, astrocytes, microvascular endothelial cells | Inhibits release of pro-inflammatory cytokines (IL-1, TNF-α) and activates release of anti-inflammatory cytokines (IL-4, IL-10) | No data yet available | Current—both murine and human studies |
| A2AR | G protein-coupled receptor | Microglia, astrocytes, neurones | Anti-inflammatory effects | No data yet available | Current—human studies |
| β-Glucuronidase | Lysosomal enzyme | Microglia, astrocytes, neurones | Anti-inflammatory effects | No data yet available | Current—murine model |
| MMPs | Immature cytoplasmic enzymes which are activated extracellularly | Microglia, astrocytes, neurones, oliodendrocytes | CNS development, e.g. neurogenesis and axonal guidance | No data yet available | Current—murine model |
| α4β2 nAChR | Pentameric nicotinic receptor | Microglia, neurones | Anti-inflammatory effects | No data yet available | Current—murine model |
| iNOS | Cytoplasmic enzyme | Microglia, astrocytes, macrophages | Nitric oxide production by immune cells | Potentially specific for the M1 phenotype | Proposed |
| IDO-1 | Cytoplasmic enzyme | Microglia, neurones | Tryptophan catalisation | No data yet available | Proposed |
| KMO | Cytoplasmic enzyme | Microglia, macrophages | Tryptophan catalisation | No data yet available | Proposed |
| FR-β | Surface receptor | Microglia | Captation and internalisation of folic acid | Potentially specific for the M2 phenotype | Proposed |
| P2Y12R | Purinergic G protein-coupled receptor | Microglia | Role in platelet aggregation | Potentially specific for the M2 phenotype | Proposed |
COX cyclooxygenase; P2X7R purinergic receptor two ion channel receptor; CB2R cannabinoid receptor type 2; A2AR adenosine receptor 2A; MMP Matrix metalloproteinases; nAChR nicotinic acetylcholine receptor; iNOS inducible nitric oxide synthase; IDO-1 indoleamine 2,3-dioxygenase 1; KMO kynurenine-3-monooxygenase; FR-β folate receptor β; P2Y12 purinergic ion channel Y12; IL interleukin; ROS reactive oxygen species; TNF-α tumour necrosis factor-α; M1 pro-inflammatory activated microglia; M2: anti-inflammatory microglia