Imaging of CNS myelin by positron-emission tomography.
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.
Stankoff
Bruno
B
Institut National de la Santé et de la Recherche Médicale, U711, Hôpital de la Salpêtrière, F-75013 Paris, France. bruno.stankoff@psl.aphp.fr
Wang
Yanming
Y
Bottlaender
Michel
M
Aigrot
Marie-Stephane
MS
Dolle
Frederic
F
Wu
Chunying
C
Feinstein
Douglas
D
Huang
Guo-Feng
GF
Semah
Frank
F
Mathis
Chester A
CA
Klunk
William
W
Gould
Robert M
RM
Lubetzki
Catherine
C
Zalc
Bernard
B
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
C513133:1,4-bis(4-aminostyryl)-2-methoxybenzene; D000840:Anisoles; D015415:Biomarkers; D002250:Carbon Radioisotopes; D005456:Fluorescent Dyes; D013267:Stilbenes; C060998:anisole