PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB

  • Daniele de Paula Faria
  • Sjef Copray
  • Jurgen W. A. Sijbesma
  • Antoon T. M. Willemsen
  • Carlos A. Buchpiguel
  • Rudi A. J. O. Dierckx
  • Erik F. J. de Vries
Original Article



In this study, we compared the ability of [11C]CIC, [11C]MeDAS and [11C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake.


Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group).


The kinetics of [11C]CIC, [11C]MeDAS and [11C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [11C]CIC make this tracer less suitable for in vivo PET imaging. [11C]PIB showed good uptake in the white matter in the cerebrum, but [11C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [11C]MeDAS distribution correlated well with myelin density in different brain regions.


This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [11C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [11C]CIC and [11C]PIB.


Demyelination Remyelination PET imaging Myelin Multiple sclerosis 


  1. 1.
    Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372:1502–17.PubMedCrossRefGoogle Scholar
  2. 2.
    Franklin RJ, Ffrench-Constant C. Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci. 2008;9:839–55.PubMedCrossRefGoogle Scholar
  3. 3.
    Taveggia C, Feltri ML, Wrabetz L. Signals to promote myelin formation and repair. Nat Rev Neurol. 2010;6:276–87.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Pillipi M, Rocca MA. MR imaging of multiple sclerosis. Radiology. 2011;259:659–81.CrossRefGoogle Scholar
  5. 5.
    Wu C, Tian D, Feng Y, Polak P, Wei J, Sharp A, et al. A novel fluorescent probe that is brain permeable and selectively binds to myelin. J Histochem Cytochem. 2006;54:997–1004.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Wang Y, Wu C, Caprariello AV, Somoza E, Zhu W, Wang C, et al. In vivo quantification of myelin changes in the vertebrate nervous system. J Neurosci. 2009;29:14663–9.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Wu C, Wang C, Popescu DC, Zhu W, Somoza EA, Zhu J, et al. A novel PET marker for in vivo quantification of myelination. Bioorg Med Chem. 2010;18:8592–9.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Wu C, Zhu J, Baeslack J, Zaremba A, Hecker J, Kraso J, et al. Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord. Ann Neurol. 2013;74:688–98.PubMedCrossRefGoogle Scholar
  9. 9.
    Stankoff B, Freeman L, Aigrot MS, Chardain A, Dollé F, Willians A, et al. Imaging central nervous system by positron emission tomography in multiple sclerosis using [methyl-11C]-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole. Ann Neurol. 2011;69(4):673–80.PubMedCrossRefGoogle Scholar
  10. 10.
    Solbach C, Uebele M, Reischl G, Machulla HJ. Efficient radiosynthesis of carbon-11 labelled uncharged Thioflavin T derivatives using [11C]methyl triflate for beta-amyloid imaging in Alzheimer’s disease with PET. Appl Radiat Isot. 2005;62:591–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab. 2005;25:1528–47.PubMedCrossRefGoogle Scholar
  12. 12.
    Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain. 2006;129:2856–66.PubMedCrossRefGoogle Scholar
  13. 13.
    Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55:306–19.PubMedCrossRefGoogle Scholar
  14. 14.
    Fodero-Tavolett MT, Rowe CC, McLean CA, Leone L, Li QX, Masters CL, et al. Characterization of PIB binding to white matter in Alzheimer disease and other dementias. J Nucl Med. 2009;50:198–204.CrossRefGoogle Scholar
  15. 15.
    Lammertsma AA. Receptor kinetics – modelling and practical approach. In: Maguire RP, Leenders KL, editors. Course manual. PET pharmacokinetic course, 17–19 May, Kobe, Japan. International Society for Cerebral Blood Flow and Metabolism; 2007. p. 65–81Google Scholar
  16. 16.
    Hall SM. The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci. 1972;10:535–46.PubMedGoogle Scholar
  17. 17.
    Waxman SG, Kocsis JD, Nitta KC. Lysophosphatidyl choline-induced focal demyelination in the rabbit corpus callosum. J Neurol Sci. 1979;44:45–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Woodruff RH, Franklin RJ. Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: a comparative study. Glia. 1999;25:216–28.PubMedCrossRefGoogle Scholar
  19. 19.
    McDonald WI, Ron MA. Multiple sclerosis: the disease and its manifestations. Philos Trans R Soc Lond B Biol Sci. 1999;354:1615–22.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Daniele de Paula Faria
    • 1
    • 2
    • 3
  • Sjef Copray
    • 2
  • Jurgen W. A. Sijbesma
    • 1
  • Antoon T. M. Willemsen
    • 1
  • Carlos A. Buchpiguel
    • 3
  • Rudi A. J. O. Dierckx
    • 1
  • Erik F. J. de Vries
    • 1
  1. 1.Department of Nuclear Medicine and Molecular ImagingUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
  2. 2.Department of NeuroscienceUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
  3. 3.Center of Nuclear MedicineUniversity of Sao Paulo, University of Sao Paulo Medical SchoolSao PauloBrazil

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