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PET imaging of P2X₇R in the experimental autoimmune encephalomyelitis model of multiple sclerosis using [¹¹C]SMW139

https://doi.org/10.1186/s12974-020-01962-7

 Summary

Neuroinflammation plays a central role in a variety of pathologies affecting the central nervous system (CNS), such as multiple sclerosis (MS), Alzheimer’s and Parkinson’s disease. Microglia are major contributor in disease’s pathogenesis, although the exact role of microglia and their activation status during the disease process is not understood exactly.

In this article the process of neuroinflammation has been studied in Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model for MS.

Mediso nanoScan PET/CT and nanoScan PET/MRI were used for non-invasive imaging of the activation status of microglia and the ability to identify a pro- or anti-inflammatory environment.

The authors have used a C-11 isotope labelled purinergic receptor (P2X₇R) ligand ([¹¹C]SMW139) for tracing microglial activity. They assessed the tracer’s potential for imaging neuroinflammation and its specific binding to P2X₇R. They also matched the molecular imaging result with autoradiography and immunohistochemistry.

The authors have shown that [11C]SMW139 is a promising PET tracer for imaging neuroinflammation and evaluating the dynamics of pro-inflammatory microglia in the brain.

Selected results from nanoScan PET/MRI and nanoScan PET/CT

• They evaluated the uptake of [¹¹C]SMW139 at the peak of inflammation and compared it to the uptake in the recovery phase.

Fig 1. Sagittal PET images extracted from the static reconstruction of the 5–45 min frame and showing [¹¹C]SMW139 uptake in the brain and spinal cord (arrows) of severe-relapsing (a), severe acute (b). Arrow heads are showing [¹¹C]SMW139 uptake in a brain draining lymph node

Fig 2. Sagittal PET images extracted from the static reconstruction of the 5–45 min frame and showing [¹¹C]SMW139 uptake in the brain and spinal cord (arrows) of relapsing EAE rat (peak of the disease (e), relapse (f), recovery (g)) and non-relapsing rat ( of the disease (h), no-relapse (i), recovery (j)). S.C. spinal cord, CB cerebellum, B.S. brain stem. Data are expressed as percent injected dose per milliliter (%ID/mL)

• They validated the specificity of [¹¹C]SMW139 tracer binding to the EAE tissue

Fig 3. Correlation between uptake of [¹¹C]SMW139 tracer in the brain of the EAE animal and the ex vivo immunostaining for IBA-1 and ED-1; Transversal (A) and sagittal (D) PET image section showing the uptake of the [¹¹C]SMW139 in the brain. The dotted purple circles or rectangles mark the area with the highest uptake. The green and red spots in the brain indicate a high accumulation of [¹¹C]SMW139; Immunostaining with IBA-1 (B, E) and CD68 (C, F) of the respective brain region post PET imaging showing high microglia activation in the same region where the high uptake of [¹¹C]SMW139 was observed by PET imaging.