Design, Synthesis, and Evaluation of Fluorinated Radioligands for Myelin Imaging

作者：Tiwari, Anand Dev; Wu, Chunying; Zhu, Junqing; Zhang, Sheng; Zhu, Jinle; Wang, William R.; Zhang, Jinming; Tatsuoka, Curtis; Matthews, Paul M.; Miller, Robert H.; Wang, Yanming^*

来源：Journal of Medicinal Chemistry, 2016, 59(8): 3705-3718.

DOI：10.1021/acs.jmedchem.5b01858

• POSITRON-EMISSION-TOMOGRAPHY
• MULTIPLE-SCLEROSIS
• NERVOUS-SYSTEM
• WHITE-MATTER
• SPINAL-CORD
• RAT MODEL
• DEMYELINATION
• REMYELINATION
• DISEASE
• BRAIN

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 ([F-18]PMeDAS, 32) with promising in vivo binding properties, which was subsequently validated by ex vivo autoradiography.

• 出版日期2016-4-28
• 单位中国人民解放军总医院