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: Bruno Stankoff, Yanming Wang, Michel Bottlaender, Marie-Stephane Aigrot, Frederic Dolle, Chunying Wu, Douglas Feinstein, Guo-Feng Huang, Frank Semah, Chester A Mathis, William Klunk, Robert M Gould, Catherine Lubetzki, Bernard Zalc
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 103 Issue 24 Pg. 9304-9 (Jun 13 2006) ISSN: 0027-8424 [Print] United States
• PMID: 16754874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,4-bis(4-aminostyryl)-2-methoxybenzene
• Anisoles
• Biomarkers
• Carbon Radioisotopes
• Fluorescent Dyes
• Stilbenes
• anisole

Topics

• Animals
• Anisoles (chemistry, metabolism)
• Biomarkers (metabolism)
• Carbon Radioisotopes (metabolism)
• Central Nervous System (anatomy & histology)
• Encephalomyelitis, Autoimmune, Experimental (metabolism, pathology)
• Fluorescent Dyes (chemistry, metabolism)
• Humans
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Multiple Sclerosis (diagnosis, pathology)
• Myelin Sheath (metabolism, pathology)
• Papio anubis
• Positron-Emission Tomography
• Rats
• Rats, Wistar
• Stilbenes (chemistry, metabolism)