title: Design, Synthesis, and Evaluation of Fluorinated Radioligands for Myelin Imaging.
abstract: Myelination is one of the fundamental processes in vertebrates. A major challenge is to quantitatively image myelin distribution in the central nervous system. For this reason, we designed and synthesized a series of fluorinated radioligands that can be radiolabeled as radiotracers for positron emission tomography (PET) imaging of myelin. These newly developed radioligands readily penetrate the blood-brain barrier and selectively bind to myelin membranes in the white matter region. Structure-activity relationship studies of such ligands suggested that optimal permeability could be achieved with calculated lipophilicty in the range of 3-4. After radiolabeling with fluorine-18, the brain uptake and retention of each radioligand were determined by microPET/CT imaging studies. These pharmacokinetic studies led us to identify a lead compound ([(18)F]FMeDAS, 32) with promising in vivo binding properties, which was subsequently validated by ex vivo autoradiography.
authors.forename: Anand Dev
authors.initials: AD
authors.lastname: Tiwari
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhu
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Jinle
authors.initials: J
authors.lastname: Zhu
authors.forename: William R
authors.initials: WR
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, People's Liberation Army (PLA) General Hospital , Beijing 100853, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.forename: Curtis
authors.initials: C
authors.lastname: Tatsuoka
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London , London SW12 0NN, United Kingdom.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.affiliation: Department of Anatomy and Regenerative Biology, George Washington University , Washington, DC 20037, United States.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001345:Autoradiography; D015195:Drug Design; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D051379:Mice; D064847:Multimodal Imaging; D009186:Myelin Sheath / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013329:Structure-Activity Relationship; D014057:Tomography, X-Ray Computed
chemical_list: D005462:Fluorine Radioisotopes