7647
doi
10.1523/JNEUROSCI.2900-11.2012
oai:zenodo.org:7647
user-inmind
user-eu
Thézé, Benoit
Inserm, Unité 1023, Université Paris Sud, 91400 Orsay, France, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Maroy, Renaud
Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Dubois, Albertine
Inserm, Unité 1023, Université Paris Sud, 91400 Orsay, France, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Brulon, Vincent
Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Fontyn, Yoann
Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Dollé, Frédéric
Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Tavitian, Bertrand
Inserm, Unité 1023, Université Paris Sud, 91400 Orsay, France, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Boisgard, Raphael
Inserm, Unité 1023, Université Paris Sud, 91400 Orsay, France, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
Imaging Microglial/Macrophage Activation in Spinal Cords of Experimental Autoimmune Encephalomyelitis Rats by Positron Emission Tomography Using the Mitochondrial 18kDa Translocator Protein Radioligand [18F]DPA-714
Abourbeh, Galith
Inserm, Unité 1023, Université Paris Sud, 91400 Orsay, France, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, 91405 Orsay, France
info:eu-repo/semantics/openAccess
Creative Commons Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/legalcode
<p>Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated microglia/macrophages play a key role in the immunopathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Microglia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of microglial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuroinflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [18F]DPA-714 [<em>N,N</em>-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [18F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [18F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (<em>R,S</em>)-PK11195 [(<em>R</em>,<em>S</em>)-<em>N</em>-methyl-<em>N</em>-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [18F]DPA-714, neuroinflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuroinflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuroinflammation for detection, monitoring, and research in MS.</p>
Zenodo
2012-04-25
info:eu-repo/semantics/article
641706
user-inmind
user-eu
award_title=Imaging of Neuroinflammation in Neurodegenerative Diseases; award_number=278850; award_identifiers_scheme=url; award_identifiers_identifier=https://cordis.europa.eu/projects/278850; funder_id=00k4n6c32; funder_name=European Commission;
1579531838.239759
1649943
md5:dde09ce77a0e953aabaad79de9c1f973
https://zenodo.org/records/7647/files/Abourbeh_JNeuroSci_2012_P08.pdf
public
The Journal of Neuroscience
32
17
5728-5736
2012-04-25