Sphingosine-1 Phosphate -Receptor Targeting and Microglial Activation

Does Targeting of Sphingosine-1 Phosphate Receptors Reduce Microglial Activation in Multiple Sclerosis? A [11C]PK11195 Brain PET Study

To evaluate the usability of positron emission tomography imaging as a novel outcome measure in multiple sclerosis studies

Background and Rationale

In multiple sclerosis (MS), significant pathology correlating to disease progression, to expanded disability status scale (EDSS) and to cognitive decline, takes place outside the plaque areas, i.e. in areas of normal appearing white matter and gray matter. Neuropathological studies suggest that mechanisms involved in this widespread pathology include activation of microglial cells, oxidative stress and deficiency in mitochondrial functions. Activated microglia can be detected in vivo with a translocator protein (TSPO), expressed in activated, but not resting microglia) binding radioligands and positron emission tomography (PET). 11Carbon-PK11195 radioligand is one such radioligand. Importantly, the possible effect of MS therapies on microglial activity can be evaluated in patients in vivo with PET-imaging performed before and after the treatment.

Inclusion Criteria:

Having signed the informed consent of the investigator-initiated PET study

• Age 18 - 58 years at the time of informed consent.
• MS according to Poser or McDonald criteria
• EDSS score from 0.0 to 6.5.
• Moderate to heavy lesion load ( >9 T2 lesions) in MRI

Exclusion Criteria:

• - Patients with other neurodegenerative disease than MS
• Disease modifying therapy (DMT) within 4 weeks of imaging
• Corticosteroid treatment within 4 weeks of imaging
• Patients with significant abnormal findings other than MS in the screening MRI.
• Patients with claustrophobia, or a history of moderate to severe anxiety disorder or panic attacks (which could potentially lead to preterm termination of the imaging)
• Contraindication to PET scan investigations
• Exposure to experimental radiation in the past 12 months such that radiodosimetry limits would be exceeded by participating in this study.
• Intolerance to previous PET scans; i.e. previous hypersensitivity reactions to any PET ligand or imaging agent or failure to participate in and comply with previous PET scans.