[C-11]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis

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Citações na Scopus
12
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article
Data de publicação
2019
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Título do Volume
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ELSEVIER SCI LTD
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MULTIPLE SCLEROSIS AND RELATED DISORDERS, v.35, p.108-115, 2019
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Resumo
Background: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C-11]PIB is widely used for detection of beta-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C-11]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of re-combinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C-11]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis. Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C-11]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C-11]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C-11]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r(2) = 0.32, P < 0.0001) and the rhMOG/CFA group (r(2) = 0.46, P < 0.0001). Conclusion: [C-11]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.
Palavras-chave
Multiple sclerosis, EAE marmoset model, PET imaging, Pittsburgh compound B
Referências
  1. Amato MP, 2007, ARCH NEUROL-CHICAGO, V64, P1157, DOI 10.1001/archneur.64.8.1157
  2. Amato MP, 2004, NEUROLOGY, V63, P89, DOI 10.1212/01.WNL.0000129544.79539.D5
  3. Baker D, 2014, MULT SCLER RELAT DIS, V3, P555, DOI 10.1016/j.msard.2014.05.002
  4. Brugarolas P, 2018, MOL IMAGING, V17, DOI 10.1177/1536012118785471
  5. Faria DD, 2014, MULT SCLER J, V20, P1443, DOI 10.1177/1352458514526941
  6. Faria DD, 2014, EUR J NUCL MED MOL I, V41, P995, DOI 10.1007/s00259-013-2682-6
  7. Faria DD, 2014, NEUROIMAGE, V87, P395, DOI 10.1016/j.neuroimage.2013.10.057
  8. Fodero-Tavoletti MT, 2009, J NUCL MED, V50, P198, DOI 10.2967/jnumed.108.057984
  9. Huang SL, 2017, RADIOLOGY, V282, P113, DOI 10.1148/radiol.2016160095
  10. Inglese M, 2010, NMR BIOMED, V23, P865, DOI 10.1002/nbm.1515
  11. Jagessar SA, 2015, J NEUROINFLAMM, V12, DOI 10.1186/s12974-015-0378-5
  12. Jagessar SA, 2012, J NEUROIMMUNE PHARM, V7, P557, DOI 10.1007/s11481-012-9384-x
  13. Kalinowska-Lyszczarz A, 2018, LUPUS, V27, P610, DOI 10.1177/0961203317735186
  14. Kangarlu A, 2007, AM J NEURORADIOL, V28, P262
  15. Lassmann H, 2012, NAT REV NEUROL, V8, P647, DOI 10.1038/nrneurol.2012.168
  16. Le Foll B, 2007, J NUCL MED, V48, P1492, DOI 10.2967/jnumed.107.039776
  17. Ntranos A, 2016, CURR NEUROL NEUROSCI, V16, DOI 10.1007/s11910-016-0688-8
  18. Oguz K.K, 2009, AM J NEURORADIOL, V30, P6
  19. Portaccio E, 2006, J NEUROL SCI, V245, P195, DOI 10.1016/j.jns.2005.07.019
  20. Reich DS, 2018, NEW ENGL J MED, V378, P169, DOI 10.1056/NEJMra1401483
  21. Stankoff B, 2011, ANN NEUROL, V69, P673, DOI 10.1002/ana.22320
  22. Steinman L, 2005, TRENDS IMMUNOL, V26, P565, DOI 10.1016/j.it.2005.08.014
  23. 't Hart BA, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.00804
  24. 't Hart BA, 2011, TRENDS MOL MED, V17, P119, DOI 10.1016/j.molmed.2010.11.006
  25. t'Hart BA, 2000, IMMUNOL TODAY, V21, P290, DOI 10.1016/S0167-5699(00)01627-3
  26. Yang FY, 2015, BRAIN STIMUL, V8, P465, DOI 10.1016/j.brs.2014.11.017
  27. Yang L, 2016, NEUROCHEM RES, V41, P1845, DOI 10.1007/s11064-016-1920-2
  28. Yuasa S, 2010, STEREOTAXIC ATLAS MA