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PET visualization of microglia in multiple sclerosis patients using [11C]PK11195
J C Debruyne1, J Versijpt, K J Van Laere
1Department of Neurology, Ghent University Hospital, Ghent, Belgium. jan.debruyne@rug.ac.be
Abstract:
Activated microglia are involved in the immune response of multiple sclerosis (MS). The peripheral benzodiazepine receptor (PBR) is expressed on microglia and up-regulated after neuronal injury. [11C]PK11195 is a positron emission tomography (PET) radioligand for the PBR. The objective of the present study was to investigate [11C]PK11195 imaging in MS patients and its additional value over magnetic resonance imaging (MRI) concerning the immuno-pathophysiological process. Seven healthy and 22 MS subjects were included. Semiquantitative [11C]PK11195 uptake values were assessed with normalization on cortical grey matter. Uptake in Gadolinium-lesions was significantly increased compared with normal white matter. Uptake in T2-lesions was generally decreased, suggesting a PBR down-regulation. However, uptake values increased whenever a clinical or MR-relapse was present, suggestive for a dynamic process with a transient PBR up-regulation. During disease progression, an increase of normal-appearing white matter (NAWM) uptake was found, propagating NAWM as the possible real burden of disease. In conclusion, [11C]PK11195 and PET are able to demonstrate inflammatory processes with microglial involvement in MS.
Insights
Positron emission tomography (PET) imaging with [11C]PK11195 reveals activated microglia in multiple sclerosis (MS). This technique offers insights into the disease
Area of Science:
- Neuroimmunology
- Radiochemistry
- Medical Imaging
Background:
- Activated microglia play a key role in multiple sclerosis (MS) pathogenesis.
- Peripheral benzodiazepine receptors (PBR) are markers of microglial activation, upregulated post-neuronal injury.
- [11C]PK11195 is a positron emission tomography (PET) radioligand targeting PBR.
Purpose of the Study:
- To evaluate [11C]PK11195 PET imaging in MS patients.
- To assess the added value of [11C]PK11195 PET over MRI in understanding MS immuno-pathophysiology.
Main Methods:
- PET imaging using the PBR-targeting radioligand [11C]PK11195.
- Inclusion of 22 MS patients and 7 healthy controls.
- Semiquantitative assessment of [11C]PK11195 uptake, normalized to cortical grey matter.
Main Results:
- [11C]PK11195 uptake was significantly increased in Gadolinium-enhancing lesions compared to normal white matter.
- T2-lesions generally showed decreased uptake, indicating PBR downregulation.
- Uptake increased during clinical or MR relapses, suggesting transient PBR upregulation.
- Increased uptake in normal-appearing white matter (NAWM) during disease progression suggests NAWM as a key disease burden.
Conclusions:
- [11C]PK11195 PET imaging effectively demonstrates microglial activation and inflammatory processes in MS.
- PET imaging provides valuable insights into the dynamic immuno-pathophysiological changes in MS.
- NAWM PBR expression may represent a significant component of the overall MS disease burden.