title: Myelin imaging compound (MIC) enhanced magnetic resonance imaging of myelination.
abstract: The vertebrate nervous system is characterized by myelination, a fundamental biological process that protects the axons and facilitates electric pulse transduction. Damage to myelin is considered a major effect of autoimmune diseases such as multiple sclerosis (MS). Currently, therapeutic interventions are focused on protecting myelin integrity and promoting myelin repair. These efforts need to be accompanied by an effective imaging tool that correlates the disease progression with the extent of myelination. To date, magnetic resonance imaging (MRI) is the primary imaging technique to detect brain lesions in MS. However, conventional MRI cannot differentiate demyelinated lesions from other inflammatory lesions and therefore cannot predict disease progression in MS. To address this problem, we have prepared a Gd-based contrast agent, termed MIC (myelin imaging compound), which binds to myelin with high specificity. In this work, we demonstrate that MIC exhibits a high kinetic stability toward transmetalation with promising relaxometric properties. MIC was used for in vivo imaging of myelination following intracerebroventricular infusion in the rat brain. MIC was found to distribute preferentially in highly myelinated regions and was able to detect regions of focally induced demyelination.
authors.affiliation: Department of Radiology, Case Center for Imaging Research, Division of Radiopharmaceutical Science, Case Western Reserve University, Cleveland, Ohio 44106, United States.
authors.forename: Luca
authors.initials: L
authors.lastname: Frullano
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhu
authors.forename: Changning
authors.initials: C
authors.lastname: Wang
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism; D005682:Gadolinium; D057967:Infusions, Intraventricular; D008279:Magnetic Resonance Imaging / Q000379:methods; D009186:Myelin Sheath / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D005682:Gadolinium
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