Central nervous system expression and PET imaging of the translocator protein in relapsing–remitting experimental autoimmune encephalomyelitis

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dc.contributor.authorMattner, Fen_AU
dc.contributor.authorStaykova, Men_AU
dc.contributor.authorBerghofer, PJen_AU
dc.contributor.authorWong, HJen_AU
dc.contributor.authorFordham, Sen_AU
dc.contributor.authorCallaghan, PDen_AU
dc.contributor.authorJackson, Ten_AU
dc.contributor.authorPham, TQen_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorZahra, Den_AU
dc.contributor.authorRahardjo, GLen_AU
dc.contributor.authorLinares, Den_AU
dc.contributor.authorKatsifis, Aen_AU
dc.date.accessioned2020-03-22T20:49:47Zen_AU
dc.date.available2020-03-22T20:49:47Zen_AU
dc.date.issued2013-01-15en_AU
dc.date.statistics2020-03-20en_AU
dc.description.abstractGlial neuroinflammation is associated with the development and progression of multiple sclerosis. PET imaging offers a unique opportunity to evaluate neuroinflammatory processes longitudinally in a noninvasive and clinically translational manner. (18)F-PBR111 is a newly developed PET radiopharmaceutical with high affinity and selectivity for the translocator protein (TSPO), expressed on activated glia. This study aimed to investigate neuroinflammation at different phases of relapsing-remitting (RR) experimental autoimmune encephalomyelitis (EAE) in the brains of SJL/J mice by postmortem histologic analysis and in vivo by PET imaging with (18)F-PBR111. METHODS: RR EAE was induced by immunization with PLP(139-151) peptide in complete Freund's adjuvant. Naive female SJL/J mice and mice immunized with saline-complete Freund's adjuvant were used as controls. The biodistribution of (18)F-PBR111 was measured in 13 areas of the central nervous system and compared with PET imaging results during different phases of RR EAE. The extents of TSPO expression and glial activation were assessed with immunohistochemistry, immunofluorescence, and a real-time polymerase chain reaction. RESULTS: There was significant TSPO expression in all of the central nervous system areas studied at the peak of the first clinical episode and, importantly, at the preclinical stage. In contrast, only a few TSPO-positive cells were observed at the second episode. At the third episode, there was again an increase in TSPO expression. TSPO expression was associated with microglial cells or macrophages without obvious astrocyte labeling. The dynamics of (18)F-PBR111 uptake in the brain, as measured by in vivo PET imaging and biodistribution, followed the pattern of TSPO expression during RR EAE. CONCLUSION: PET imaging with the TSPO ligand (18)F-PBR111 clearly reflected the dynamics of microglial activation in the SJL/J mouse model of RR EAE. The results are the first to highlight the discrepancy between the clinical symptoms of EAE and TSPO expression in the brain, as measured by PET imaging at the peaks of various EAE episodes. The results suggest a significant role for PET imaging investigations of neuroinflammation in multiple sclerosis and allow for in vivo follow-up of antiinflammatory treatment strategies. © 2013 Society of Nuclear Medicine and Molecular Imaging, Inc.en_AU
dc.identifier.citationMattner, F., Staykova, M., Berghofer, P., Wong, H. J., Fordham, S., Callaghan, P., Jackson, T., Pham, T., Grégoire, M. C., Zahra, D., Rahardjo, G., Linares, D., & Katsifis, A. G. (2013). Central nervous system expression and pet imaging of the translocator protein in relapsing–remitting experimental autoimmune encephalomyelitis. Journal of Nuclear Medicine, 54(2), 291-298. doi:10.2967/jnumed.112.108894en_AU
dc.identifier.govdoc8811en_AU
dc.identifier.issn0161-5505en_AU
dc.identifier.issue2en_AU
dc.identifier.journaltitleJournal of Nuclear Medicineen_AU
dc.identifier.pagination291-298en_AU
dc.identifier.urihttps://doi.org/10.2967/jnumed.112.108894en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9177en_AU
dc.identifier.volume54en_AU
dc.language.isoenen_AU
dc.publisherSociety of Nuclear Medicine and Molecular Imagingen_AU
dc.subjectProteinsen_AU
dc.subjectBrainen_AU
dc.subjectCentral nervous systemen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectInflammationen_AU
dc.subjectMiceen_AU
dc.subjectAntipyreticsen_AU
dc.titleCentral nervous system expression and PET imaging of the translocator protein in relapsing–remitting experimental autoimmune encephalomyelitisen_AU
dc.typeJournal Articleen_AU
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