title: In vivo quantification of myelin changes in the vertebrate nervous system.
abstract: Destruction or changes associated with myelin membranes in the CNS play a key role in the pathogenesis of multiple sclerosis and other related neurodegenerative disorders. A long-standing goal has been to detect and quantify myelin content in vivo. For this reason, we have developed a myelin-imaging technique based on positron emission tomography (PET). PET is a quantitative imaging modality that has been widely used in clinical settings for direct assessment of biological processes at the molecular level. However, lack of myelin-imaging probes has hampered the use of PET for imaging of myelination in the CNS. Here, we report a myelin-imaging agent, termed Case Imaging Compound (CIC) that readily penetrates the blood-brain barrier and preferentially localizes to myelinated regions of the brain. After radiolabeling with positron-emitting carbon-11, [(11)C]CIC-PET was conducted in longitudinal studies using a lysolethicin-induced rat model of focal demyelination and subsequent remyelination. Quantitative analysis showed that the retention of [(11)C]CIC correlates with the level of demyelination/remyelination. These studies indicate that, for the first time, [(11)C]CIC-PET can be used as an imaging marker of myelination, which has the potential to be translated into clinical studies in multiple sclerosis and other myelin-related diseases for early diagnosis, subtyping, and efficacy evaluation of therapeutic treatments aimed at myelin repair.
authors.affiliation: Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, and Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA. yanming.wang@case.edu
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Caprariello
authors.forename: Eduardo
authors.initials: E
authors.lastname: Somoza
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhu
authors.forename: Changning
authors.initials: C
authors.lastname: Wang
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000502:physiology*; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000502:physiology; D003711:Demyelinating Diseases / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D008137:Longitudinal Studies; D051379:Mice; D008959:Models, Neurological; D009186:Myelin Sheath / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000502:physiology*; D049268:Positron-Emission Tomography / Q000592:standards; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results