Neuroinflammation following disease modifying therapy in multiple sclerosis: A pilot positron emission tomography study

J Neurol Sci. 2018 Feb 15:385:30-33. doi: 10.1016/j.jns.2017.12.004. Epub 2017 Dec 6.

Abstract

Introduction: Chronic activation of microglia accelerates the neurodegenerative process in multiple sclerosis (MS). Although disease modifying therapy (DMT) is reportedly effective for neuroinflammatory responses in MS, the progression of neuroinflammation after DMT remains unclear.

Methods: We evaluated microglial activation in six clinically stable relapsing-remitting MS patients after DMT by quantifying changes in translocator protein (TSPO) density using PET with [11C]DPA713, a selective TSPO tracer for microglial activation. All patients underwent [11C]DPA713 PET scans twice, and the scans were conducted one year apart. The binding potential (BPND) of the tracer was estimated using a simplified reference tissue model.

Results: [11C]DPA713 BPND measured at 6months after DMT was significantly higher in the MS group than that in the control group. Compared with the first PET measurement, the one-year PET measurement revealed significantly elevated [11C]DPA713 BPND in broader brain regions covering the temporal and parietal cortices after one year of DMT.

Conclusions: The current results indicate that microglial activation may proceed in the entire brain of clinically stable MS patients even after receiving DMT.

Keywords: Disease modifying therapy; Microglia; Multiple sclerosis; Positron emission tomography; TSPO; [(11)C]DPA713.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / adverse effects*
  • Brain / diagnostic imaging
  • Carbon Isotopes / pharmacokinetics
  • Disability Evaluation
  • Encephalitis / chemically induced*
  • Encephalitis / diagnostic imaging
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / drug therapy*
  • Pilot Projects
  • Positron-Emission Tomography*
  • Pyrazoles / pharmacokinetics
  • Pyrimidines / pharmacokinetics

Substances

  • Antirheumatic Agents
  • Carbon Isotopes
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • Pyrazoles
  • Pyrimidines