Cited by 114Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

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In Vivo Detection of Age- and Disease-Related Increases in Neuroinflammation by18F-GE180 TSPO MicroPET Imaging in Wild-Type and Alzheimer's Transgenic Mice

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Liu, Bin, Le, Kevin X., Park, Mi-Ae, Wang, Shuyan, Belanger, Anthony P., Dubey, Shipra, Frost, Jeffrey L., Holton, Peter, Reiser, Vladimir, Jones, Paul A., Trigg, William, Di Carli, Marcelo F., Lemere, Cynthia. A.·2015·The Journal of Neuroscience

DOI 10.1523/jneurosci.0996-15.2015PMC PMC6705465

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Abstract

Alzheimer's disease (AD) is the most common cause of dementia. Neuroinflammation appears to play an important role in AD pathogenesis. Ligands of the 18 kDa translocator protein (TSPO), a marker for activated microglia, have been used as positron emission tomography (PET) tracers to reflect neuroinflammation in humans and mouse models. Here, we used the novel TSPO-targeted PET tracer 18 F-GE180 (flutriciclamide) to investigate differences in neuroinflammation between young and old WT and APP/PS1dE9 transgenic (Tg) mice.In vivo PET scans revealed an overt age-dependent elevation in whole-brain uptake of 18 F-GE180 in both WT and Tg mice, and a significant increase in whole-brain uptake of 18 F-GE180 (peak-uptake and retention) in old Tg mice compared with young Tg mice and all WT mice. Similarly, the 18 F-GE180 binding potential in hippocampus was highest to lowest in old Tg > old WT > young Tg > young WT mice using MRI coregistration.Ex vivo PET and autoradiography analysis further confirmed our in vivo PET results: enhanced uptake and specific binding (SUV 75%) of 18 F-GE180 in hippocampus and cortex was highest in old Tg mice followed by old WT, young Tg, and finally young WT mice.18 F-GE180 specificity was confirmed by an in vivo cold tracer competition study. We also examined 18 F-GE180 metabolites in 4-month-old WT mice and found that, although total radioactivity declined over 2 h, of the remaining radioactivity, ∼90% was due to parent 18 F-GE180. In conclusion,18 F-GE180 PET scans may be useful for longitudinal monitoring of neuroinflammation during AD progression and treatment. SIGNIFICANCE STATEMENT Microglial activation, a player in Alzheimer's disease (AD) pathogenesis, is thought to reflect neuroinflammation. Using in vivo microPET imaging with a novel TSPO radioligand,18 F-GE180, we detected significantly enhanced neuroinflammation during normal aging in WT mice and in response to AD-associated pathology in APP/PS1dE9 Tg mice, an AD mouse model. Increased uptake and specific binding of 18 F-GE180 in whole brain and hippocampus were confirmed by ex vivo PET and autoradiography. The binding specificity and stability of 18 F-GE180 was further confirmed by a cold tracer competition study and a metabolite study, respectively. Therefore,18 F-GE180 PET imaging may be useful for longitudinal monitoring of neuroinflammation during AD progression and treatment and may also be useful for other neurodegenerative diseases.

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Authors: Liu, B., Le, K. X., Park, M.-A., Wang, S., Belanger, A. P., Dubey, S., Frost, J. L., Holton, P., Reiser, V., Jones, P. A., Trigg, W., Di Carli, M. F., & Lemere, C. A.
Affiliations: Harvard University (US)
Brigham and Women's Hospital (US)
ORCID: Liu, Bin
Le, Kevin X.
Park, Mi-Ae
Wang, Shuyan
Belanger, Anthony P.
Dubey, Shipra
Jones, Paul A.
Trigg, William
Lemere, Cynthia. A.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2015-11-25
Volume: 35
Issue: 47
Pages: 15716-15730
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.0996-15.2015
PMC: PMC6705465
OpenAlex: W2253390436
Cited by: 114
References: 73
Citations by year: 2026: 3 · 2025: 4 · 2024: 12 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 11 · 2018: 14 · 2017: 17 · 2016: 9
FWCI: 7.13
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (R01AG040092)
National Institute of Neurological Disorders and Stroke (R01NS136122)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords: Alzheimer's disease, neuroinflammation, microglial activation, aging, hippocampus, microPET imaging, binding potential, tracer metabolism, Alzheimer's disease biomarkers
MeSH terms: Aging, Alzheimer Disease, Animals, Carbazoles, Fluorine Radioisotopes, Humans, Inflammation, Male, Mice, Inbred C57BL, Mice, Transgenic, Receptors, GABA, Disease Progression, Positron-Emission Tomography, Mice

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In Vivo Detection of Age- and Disease-Related Increases in Neuroinflammation by18F-GE180 TSPO MicroPET Imaging in Wild-Type and Alzheimer's Transgenic Mice

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