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.


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*


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