Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System

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• 作者：Chunying WuBrendan Eck ; Sheng Zhang ; Junqing Zhu ; Anand Dev Tiwari ; Yifan Zhang ; Yunjie Zhu ; Jinming Zhang ; Bin Wang ; Xizhen Wang ; Xu Wang ; Jingqiang You ; Jian Wang ; Yihui Guan ; Xingdang Liu ; Xin Yu ; Bruce D. Trapp ; Robert Miller ; Jerry Silver ; David Wilson ; Yanming Wang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：February 9, 2017
• 年：2017
• 卷：60
• 期：3
• 页码：987-999
• 全文大小：600K
• ISSN：1520-4804

文摘

Myelin pathology is present in many neurological conditions such as multiple sclerosis (MS) and traumatic spinal cord injury (SCI). To facilitate development of novel therapies aimed at myelin repair, we set out to develop imaging agents that permit direct quantification of myelination in vivo. In this work, we designed and synthesized a series of fluorescent fluorinated myelin imaging agents that can be used for in vivo positron emission tomography (PET) imaging combined with subsequent post-mortem fluorescent cryoimaging. Structure–activity relationship (SAR) studies of the newly developed myelin imaging agents led us to identify a lead compound (TAFDAS, 21) that readily enters the brain and spinal cord and selectively binds to myelin. By conducting sequential PET and 3D cryoimaging in an SCI rat model, we demonstrated for the first time that PET and cryoimaging can be combined as a novel technique to image the spinal cord with high sensitivity and spatial resolution.