Cited by 212Neuroinflammation and Neurodegeneration MechanismsPharmacological Receptor Mechanisms and EffectsMedical Imaging Techniques and Applications

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Evaluation of the PBR/TSPO Radioligand [ 18 F]DPA-714 in a Rat Model of Focal Cerebral Ischemia

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Martín, Abraham, Boisgard, Raphaël, Thézé, Benoit, Van Camp, Nadja, Kuhnast, Bertrand, Damont, Annelaure, Kassiou, Michael, Dollé, Frédéric, Tavitian, Bertrand·2010·Journal of Cerebral Blood Flow & Metabolism

Abstract

Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [(18)F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. In vivo PET imaging showed significant increase in DPA (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. In vitro autoradiography confirmed these in vivo results. In vivo and in vitro [(18)F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [(18)F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke.

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  1. Chen MK, 2008, Pharmacol Ther, 2008, 118
  2. Lammertsma AA, 1996, Neuroimage, 19, 312
  3. Le Pogam A, 2008, J Nucl Med, 49, 231P

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Metadata

Authors
Martín, A., Boisgard, R., Thézé, B., Van Camp, N., Kuhnast, B., Damont, A., Kassiou, M., Dollé, F., & Tavitian, B.
Affiliations
  • Inserm (FR)
  • INSERM U803, Orsay, France
  • CEA, DSV, FBM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale, Orsay, France
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
  • The University of Sydney (AU)
Corresponding author
Tavitian, Bertrand
Venue
Journal of Cerebral Blood Flow & Metabolism
Published
2009-09-30
Volume
30
Issue
1
Pages
230-241
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
OpenAlex
W1982808247
Cited by
206
References
33
Citations by year
2025: 6 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 39 · 2020: 23 · 2019: 11 · 2018: 11 · 2017: 8 · 2016: 12 · 2015: 15 · 2014: 14 · 2013: 11 · 2012: 12
FWCI
7.48
Type
journal article
Language
en
Open access
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
[18F]DPA-714, focal cerebral ischemia, stroke, neuroinflammation, microglia/macrophages, astrocytes, PET radiotracer, rat model
MeSH terms
Animals, Astrocytes, Autoradiography, Carrier Proteins, Cell Count, Brain Ischemia, Data Interpretation, Statistical, Fluorine Radioisotopes, Image Processing, Computer-Assisted, Immunohistochemistry, Inflammation, Male, Pyrazoles, Pyrimidines, Receptors, GABA-A, Models, Statistical, Rats, Sprague-Dawley, Microglia, Radiopharmaceuticals, Stroke, Positron-Emission Tomography, Rats

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