title: PET imaging of disease progression and treatment effects in the experimental autoimmune encephalomyelitis rat model.
abstract: The experimental autoimmune encephalomyelitis model is a model of multiple sclerosis that closely mimics the disease characteristics in humans. The main hallmarks of multiple sclerosis are neuroinflammation (microglia activation, monocyte invasion, and T-cell infiltration) and demyelination. PET imaging may be a useful noninvasive technique for monitoring disease progression and drug treatment efficacy in vivo.
  
  
  METHODS
  Experimental autoimmune encephalomyelitis was induced by myelin-oligodendrocyte glycoprotein immunization in female Dark Agouti rats. Experimental autoimmune encephalomyelitis rats were imaged at baseline and at days 6, 11, 15, and 19 after immunization to monitor monocyte and microglia activation ((11)C-PK11195) and demyelination ((11)C-MeDAS) during normal disease progression and during treatment with dexamethasone.
  
  
  RESULTS
  (11)C-PK11195 PET detected activation of microglia and monocytes in the brain stem and spinal cord during disease progression. The uptake of (11)C-PK11195 was elevated in dexamethasone-treated animals that had shown mild clinical symptoms that had resolved at the time of imaging. Demyelination was not detected by (11)C-MeDAS PET, probably because of the small size of the lesions (average, 0.13 mm).
  
  
  CONCLUSIONS
  PET imaging of neuroinflammation can be used to monitor disease progression and the consequences of treatment in the experimental autoimmune encephalomyelitis rat model. PET imaging was more sensitive than clinical symptoms for detecting inflammatory changes in the central nervous system.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Center of Nuclear Medicine, University of Sao Paulo Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: de Paula Faria
authors.affiliation: TNO, Zeist, The Netherlands; and.
authors.forename: Maria L H
authors.initials: ML
authors.lastname: Vlaming
authors.affiliation: Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sjef C V M
authors.initials: SC
authors.lastname: Copray
authors.affiliation: TNO, Leiden, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Tielen
authors.affiliation: TNO, Leiden, The Netherlands.
authors.forename: Herma J A
authors.initials: HJ
authors.lastname: Anthonijsz
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jurgen W A
authors.initials: JW
authors.lastname: Sijbesma
authors.affiliation: Center of Nuclear Medicine, University of Sao Paulo Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Buchpiguel
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: TNO, Leiden, The Netherlands.
authors.forename: José W A
authors.initials: JW
authors.lastname: van der Hoorn
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands e.f.j.de.vries@umcg.nl.
authors.forename: Erik F J
authors.initials: EF
authors.lastname: de Vries
mesh_terms: D000577:Amides; D000814:Aniline Compounds; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D007546:Isoquinolines; D017628:Microglia / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D009186:Myelin Sheath / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D013267:Stilbenes; D016896:Treatment Outcome
chemical_list: C504060:(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; D000577:Amides; D000814:Aniline Compounds; D007546:Isoquinolines; C000594970:N-methyl-4,4'-diaminostilbene; D013267:Stilbenes
keywords: PET imaging; demyelination; multiple sclerosis; neuroinflammation