Neuroinflammation in healthy aging: a PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [(18)F]-FEPPA

Neuroimage. 2014 Jan 1;84:868-75. doi: 10.1016/j.neuroimage.2013.09.021. Epub 2013 Sep 21.

Abstract

One of the cellular markers of neuroinflammation is increased microglia activation, characterized by overexpression of mitochondrial 18kDa Translocator Protein (TSPO). TSPO expression can be quantified in-vivo using the positron emission tomography (PET) radioligand [(18)F]-FEPPA. This study examined microglial activation as measured with [(18)F]-FEPPA PET across the adult lifespan in a group of healthy volunteers. We performed genotyping for the rs6971 TS.PO gene polymorphism to control for the known variability in binding affinity. Thirty-three healthy volunteers (age range: 19-82years; 22 high affinity binders (HAB), 11 mixed affinity binders (MAB)) underwent [(18)F]-FEPPA PET scans, acquired on the High Resolution Research Tomograph (HRRT) and analyzed using a 2-tissue compartment model. Regression analyses were performed to examine the effect of age adjusting for genetic status on [(18)F]-FEPPA total distribution volumes (VT) in the hippocampus, temporal, and prefrontal cortex. We found no significant effect of age on [(18)F]-FEPPA VT (F (1,30)=0.918; p=0.346), and a significant effect of genetic polymorphism (F (1,30)=8.767; p=0.006). This is the first in-vivo study to evaluate age-related changes in TSPO binding, using the new generation TSPO radioligands. Increased neuroinflammation, as measured with [(18)F]-FEPPA PET was not associated with normal aging, suggesting that healthy elderly individuals may serve as useful benchmark against patients with neurodegenerative disorders where neuroinflammation may be present.

Keywords: Healthy aging; Microglia activation; Neuroinflammation; PET imaging; TSPO; [(18)F]-FEPPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Anilides*
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Image Interpretation, Computer-Assisted
  • Inflammation / diagnostic imaging
  • Inflammation / metabolism
  • Male
  • Microglia / diagnostic imaging
  • Microglia / metabolism
  • Middle Aged
  • Positron-Emission Tomography
  • Pyridines*
  • Radiopharmaceuticals*
  • Receptors, GABA / analysis
  • Receptors, GABA / metabolism*

Substances

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