title: Imaging of CNS myelin by positron-emission tomography.
abstract: Promoting myelin repair is one of the most promising therapeutic avenues in the field of myelin disorders. In future clinical trials, evaluation of remyelination will require a reliable and quantifiable myelin marker to be used as a surrogate marker. To date, MRI assessment lacks specificity for evaluating the level of remyelination within the brain. Here, we describe 1,4-bis(p-aminostyryl)-2-methoxy benzene (BMB), a synthesized fluorescent molecule, that binds selectively to myelin both ex vivo and in vivo. The binding of BMB to myelin allows the detection of demyelinating lesions in an experimental autoimmune encephalitis model of demyelination and allows a mean for quantifying myelin loss in dysmyelinating mutants. In multiple sclerosis brain, different levels of BMB binding differentiated remyelination in shadow plaques from either demyelinated lesions or normal-appearing white matter. After systemic injection, BMB crosses the blood-brain barrier and binds to myelin in a dose-dependent and reversible manner. Finally, we provide evidence that (11)C-radiolabeled BMB can be used in vivo to image CNS myelin by positron-emission tomography in baboon. Our results provide a perspective for developing a brain myelin imaging technique by positron-emission tomography.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U711, Hôpital de la Salpêtrière, F-75013 Paris, France. bruno.stankoff@psl.aphp.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
authors.forename: Marie-Stephane
authors.initials: MS
authors.lastname: Aigrot
authors.forename: Frederic
authors.initials: F
authors.lastname: Dolle
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Douglas
authors.initials: D
authors.lastname: Feinstein
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Huang
authors.forename: Frank
authors.initials: F
authors.lastname: Semah
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: William
authors.initials: W
authors.lastname: Klunk
authors.forename: Robert M
authors.initials: RM
authors.lastname: Gould
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.forename: Bernard
authors.initials: B
authors.lastname: Zalc
mesh_terms: D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D002490:Central Nervous System / Q000033:anatomy & histology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D048530:Papio anubis; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism
chemical_list: C513133:1,4-bis(4-aminostyryl)-2-methoxybenzene; D000840:Anisoles; D015415:Biomarkers; D002250:Carbon Radioisotopes; D005456:Fluorescent Dyes; D013267:Stilbenes; C060998:anisole