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PET imaging of disease progression and treatment effects in the experimental autoimmune encephalomyelitis rat model

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Author: Paula Faria, D. de · Vlaming, M.L.H. · Copray, S.C.V.M. · Tielen, F. · Anthonijsz, H.J.A. · Sijbesma, J.W.A. · Buchpiguel, C.A. · Dierckx, R.A.J.O. · Hoorn, J.W.A. van der · Vries, E.F.J. de
Type:article
Date:2014
Source:Journal of Nuclear Medicine, 8, 55, 1330-1335
Identifier: 513449
doi: doi:10.2967/jnumed.114.137216
Keywords: Biology · Demyelination · Multiple sclerosis · Neuroinflammation · PET imaging · Dexamethasone acetate · MeDAS c 11 · Myelin oligodendrocyte glycoprotein · N sec butyl 1 (2 chlorophenyl) n methyl 3 isoquinolinecarboxamide c 11 · Radiopharmaceutical agent · Unclassified drug · Animal cell · Animal experiment · Animal model · Animal tissue · Brain region · Cell invasion · Controlled study · Demyelination · Disease course · Drug effect · Experimental autoimmune encephalomyelitis · Female · In vivo study · Microglia · Monocyte · Neuroimaging · Nonhuman · PET scanner · Positron emission tomography · Priority journal · Rat · Scoring system · Biomedical Innovation · Healthy Living · Life · MSB - Microbiology and Systems Biology MHR - Metabolic Health Research · ELSS - Earth, Life and Social Sciences

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 (11C-PK11195) and demyelination ( 11C-MeDAS) during normal disease progression and during treatment with dexamethasone. Results: 11C-PK11195 PET detected activation of microglia and monocytes in the brain stem and spinal cord during disease progression. The uptake of 11C-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 11C-MeDAS PET, probably because of the small size of the lesions (average, 0.13 mm). Conclusion: 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. COPYRIGHT © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.Chemicals/CAS: dexamethasone acetate, 1177-87-3