title: Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-¹¹C]-2-(4'-methylaminophenyl)- 6-hydroxybenzothiazole.
abstract: OBJECTIVE
  Imaging of myelin tracts in vivo would greatly improve the monitoring of demyelinating diseases such as multiple sclerosis (MS). To date, no imaging technique specifically targets demyelination and remyelination. Recently, amyloid markers related to Congo red have been shown to bind to central nervous system (CNS) myelin. Here we questioned whether the thioflavine-T derivative 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PIB), which also binds to amyloid plaques, could serve as a myelin marker.
  
  
  METHODS
  PIB fixation to myelin was studied by fluorescence in the normal and dysmyelinating mouse brain, as well as in the postmortem brain of MS patients. Positron emission tomography (PET) experiments were conducted using [¹¹C]PIB in baboons and in a proof of concept clinical study in 2 MS patients.
  
  
  RESULTS
  Applied directly on tissue sections or after intraperitoneal injection, PIB stained CNS myelin, and the decrease in the level of fixation paralleled the amount of myelin loss in a dysmyelinating mutant. In normally myelinated areas of postmortem MS brain, demyelinated and remyelinated lesions were clearly distinguishable by the differential intensity of labeling observed with PIB. PET using intravenously injected radiolabeled [¹¹C]PIB imaged CNS myelin in baboons and humans. In MS patients, the dynamic analysis of PET acquisitions allowed quantitative assessment of demyelination.
  
  
  CONCLUSIONS
  PIB could be used as an imaging marker to quantify myelin loss and repair in demyelinating diseases.
authors.affiliation: Inserm, U975, Paris, France; Faculty of Medicine, Pierre and Marie Curie University, Paris, France. bruno.stankoff@tnn.aphp.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.forename: Leorah
authors.initials: L
authors.lastname: Freeman
authors.forename: Marie-Stéphane
authors.initials: MS
authors.lastname: Aigrot
authors.forename: Audrey
authors.initials: A
authors.lastname: Chardain
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Anna
authors.initials: A
authors.lastname: Williams
authors.forename: Damien
authors.initials: D
authors.lastname: Galanaud
authors.forename: Lucie
authors.initials: L
authors.lastname: Armand
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehericy
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.forename: Bernard
authors.initials: B
authors.lastname: Zalc
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D002102:Cadaver; D002250:Carbon Radioisotopes; D003711:Demyelinating Diseases / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D009416:Nerve Regeneration; D048530:Papio anubis; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D013844:Thiazoles