Microglial activation in Parkinson's disease using [18F]-FEPPA

J Neuroinflammation. 2017 Jan 11;14(1):8. doi: 10.1186/s12974-016-0778-1.

Abstract

Background: Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson's disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo.

Methods: Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [18F]-FEPPA between PD patients and HC. FEPPA total distribution volume (V T) values in cortical as well as subcortical brain regions were derived from a two-tissue compartment model with arterial plasma as an input function.

Results: Our results revealed a significant main effect of genotype on [18F]-FEPPA V T in every brain region, but no main effect of disease or disease × genotype interaction in any brain region. The overall percentage difference of the mean FEPPA V T between HC-MABs and HC-HABs was 32.6% (SD = 2.09) and for PD-MABs and PD-HABs was 43.1% (SD = 1.21).

Conclusions: Future investigations are needed to determine the significance of [18F]-FEPPA as a biomarker of neuroinflammation as well as the importance of the rs6971 polymorphism and its clinical consequence in PD.

Keywords: Neuroinflammation; PET; Parkinson’s disease; TSPO imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anilides / pharmacokinetics*
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / pathology
  • Case-Control Studies
  • Female
  • Fluorine Radioisotopes / pharmacokinetics*
  • Humans
  • Male
  • Microglia / drug effects*
  • Microglia / pathology
  • Middle Aged
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology*
  • Polymorphism, Single Nucleotide / genetics
  • Positron-Emission Tomography
  • Pyridines / pharmacokinetics*
  • Receptors, GABA / genetics
  • Severity of Illness Index

Substances

  • Anilides
  • Fluorine Radioisotopes
  • N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride
  • Pyridines
  • Receptors, GABA
  • TSPO protein, human