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

Suridjan, I.; Rusjan, P.M.; Voineskos, A.N.; Selvanathan, T.; Setiawan, E.; Strafella, A.P.; Wilson, A.A.; Meyer, J.H.; Houle, S.; Mizrahi, R.

doi:10.1016/j.neuroimage.2013.09.021

Cited by 71Neuroinflammation and Neurodegeneration MechanismsMedical Imaging Techniques and ApplicationsPharmacological Receptor Mechanisms and Effects

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

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Suridjan, I., Rusjan, P.M., Voineskos, A.N., Selvanathan, T., Setiawan, E., Strafella, A.P., Wilson, A.A., Meyer, J.H. +2 more·2014·NeuroImage

DOI 10.1016/j.neuroimage.2013.09.021PMC PMC6283059

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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.

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Some PET studies have shown increased TSPO ligand-binding activity in the brains of older adults, while other studies did not.
“Although some PET studies have shown increased TSPO ligand-binding activity in the brains of older adults, other studies did not (Suridjan et al, 2014).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Suridjan et al, 2014
Discrepancies in TSPO PET findings have been attributed to difference in ligand types, off-target binding, uneven distribution of the radioactive ligand in the brain parenchyma, and tissue-dependent differences in ligand affinity.
“These discrepancies have been attributed to the difference in ligand types, off-target binding (such as the vascular endothelial cells), uneven distribution of the radioactive ligand in the brain parenchyma, and tissue-dependent differences in ligand affinity (Suridjan et al, 2014;Turkheimer et al, 2015).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Suridjan et al, 2014

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Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica
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[ 11 C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat
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Peripheral cytokine and fatty acid associations with neuroinflammation in AD and aMCI patients: An exploratory study
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Abdominal Obesity and Brain Atrophy in Type 2 Diabetes Mellitus
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Neuroimaging of translocator protein in patients with systemic lupus erythematosus: a pilot study using [ 11 C]DPA-713 positron emission tomography
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Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195
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Facile synthesis of SSR180575 and discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[18F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, a potent pyridazinoindole ligand for PET imaging of TSPO in cancer
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Quantitative imaging of neuroinflammation in human white matter: A positron emission tomography study with translocator protein 18 kDa radioligand, [18F]‐FEPPA
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Myoinositol CEST signal in animals with increased Iba-1 levels in response to an inflammatory challenge—Preliminary findings
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Kinetic isotope effects and synthetic strategies for deuterated carbon-11 and fluorine-18 labelled PET radiopharmaceuticals
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Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study
Butler, T., Wang, X. H., Chiang, G. C.-Y., Li, Y., Zhou, L., Xi, K., Wickramasuriya, N., Tanzi, E. B., Spector, E. B., Özşahin, İ., et al. (2023) · American Journal of Neuroradiology · doi:10.3174/ajnr.a7903 · Cited by 18 · see citing works
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Microglia imaging in methamphetamine use disorder: a positron emission tomography study with the 18 kDa translocator protein radioligand [F‐18]FEPPA
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Disentangling causality in brain aging: The complex interplay between glial senescence, neuroinflammation, and neurodegeneration
Suk, K. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115737 · Cited by 10 · see citing works
Microglia positron emission tomography and progression in multiple sclerosis: thalamus on fire
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Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer’s Disease with Positron Emission Tomography
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Unresponsiveness of Experimental Canine Leishmaniosis to a New Amphotericin B Formulation
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Age‐Dependent Regulation of Hippocampal Inflammation by the Mitochondrial Translocator Protein in Mice
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Highlights of articles published in annals of nuclear medicine 2016
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Activated Microglia in the Brain: Mitochondrial and Cell Membrane-Associated Targets for Positron Emission Tomography
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Development of a minimally invasive simultaneous estimation method for quantifying translocator protein binding with [18F]FEPPA positron emission tomography
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Hemispheric asymmetry of [11C](R)PK11195 binding to translocator protein 18 kDa (TSPO) in normal brain
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The neuropsychiatric features of Long COVID in older adults and the potential association with neuroinflammation: Preliminary observations in a small cohort
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Reframing brain aging: neuroinflammation as an interconnected network process
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Biomarkers of Neurotoxicity and Disease
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Exercise central haemodynamics: physiology and clinical relevance in patients with type 2 diabetes mellitus
Climie, R. (2016) · UTAS Research Repository · doi:10.25959/23242904
Neural Substrates of Parkinson's Disease
Koshimori, Y. (2016) · TSpace (University of Toronto)
Positron emission tomography imaging of neuroinflammation in Multiple Sclerosis with a second generation translocator protein PET radioligand
Colasanti, A. (2014) · Spiral (Imperial College London) · doi:10.25560/25285
Mitochondrial Function and Inflammation in Individuals at Clinical High Risk for Psychosis and Patients with Early Stage Schizophrenia
Wu, A. (2019) · TSpace (University of Toronto)
TSPO Imaging in Psychiatric Disorders
Červenka, S., & Mizrahi, R. (2020) · Springer eBooks · doi:10.1007/978-3-030-57231-0_18
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P4‐164: Mapping neuroinflammation in vivo in healthy aging and Alzheimer's disease: A PET study using a novel translocator protein 18kDA (TSPO) radioligand, [18F]‐FEPPA
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Quantitative imaging of neuroinflammation in human white matter: A positron emission tomography study with translocator protein 18 kDa radioligand, [18F]‐FEPPA
Suridjan, I., Rusjan, P., Kenk, M., Verhoeff, N. P. L. G., Voineskos, A. N., Rotenberg, D. J., Wilson, A. A., Meyer, J. H., Houle, S., & Mizrahi, R. (2014) · Synapse · doi:10.1002/syn.21765 · Cited by 20 · see citing works
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Positron emission tomography (PET) imaging of neuroinflammation in healthy and Alzheimer disease participants using TSPO tracers
Fuh, J., Lin, Y., Yeh, S. H., Lee, W., Chang, W., Chang, C., Yang, B., Peng, N., & Huang, W. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.073250 · Cited by 3 · see citing works

Authors: Suridjan, I., Rusjan, P. M., Voineskos, A. N., Selvanathan, T., Setiawan, E., Strafella, A. P., Wilson, A. A., Meyer, J. H., Houle, S., & Mizrahi, R.
Affiliations: Centre for Addiction and Mental Health (CA)
University Health Network (CA)
Corresponding author: Mizrahi, R.
ORCID: Suridjan, I.
Rusjan, P.M.
Voineskos, A.N.
Selvanathan, T.
Strafella, A.P.
Houle, S.
Mizrahi, R.
Venue: NeuroImage
Publisher: Elsevier BV
Published: 2014-01
Volume: 84
Pages: 868-875
ISSN: 1053-8119 (ISSN-L)
DOI: 10.1016/j.neuroimage.2013.09.021
PMC: PMC6283059
OpenAlex: W2028274953
Cited by: 71
References: 87
Citations by year: 2026: 4 · 2025: 5 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 6
FWCI: 4.67
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: NeuroImage (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Scottish Grant Charitable Foundation
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
Keywords: neuroinflammation, healthy aging, microglial activation, TSPO, [18F]FEPPA, PET radiotracer, binding affinity, hippocampus, prefrontal cortex, temporal cortex, volume of distribution, healthy older adults
MeSH terms: Aging, Anilides, Brain, Female, Fluorine Radioisotopes, Humans, Image Interpretation, Computer-Assisted, Inflammation, Male, Middle Aged, Pyridines, Microglia, Receptors, GABA, Radiopharmaceuticals, Positron-Emission Tomography

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

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