- Design, Synthesis, and Evaluation of Fluorinated Radioligands for Myelin Imaging
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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 ([18F]FMeDAS, 32) with promising in vivo binding properties, which was subsequently validated by ex vivo autoradiography.
- 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
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- Novel compounds useful as fluorescent probes selectively binding to tau aggregates and preparation method thereof
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A compound having high selectivity for tau aggregates and a method for preparing the same. The present invention relates to a tau targeting fluorescent probe including the compound, a composition for detecting tau fiber protein comprising the fluorescent
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Paragraph 0365-0368
(2021/01/29)
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- Novel 18F-Labeled Radioligands for Positron Emission Tomography Imaging of Myelination in the Central Nervous System
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Myelin is the protective sheath that surrounds nerves in vertebrates to protect axons, which thereby facilitates impulse conduction. Damage to myelin is associated with many neurodegenerative diseases such as multiple sclerosis and also includes spinal co
- Tiwari, Anand Dev,Zhu, Junqing,You, Jingqiang,Eck, Brendan,Zhu, Jinle,Wang, Xu,Wang, Xizhen,Wang, Bin,Silver, Jerry,Wilson, David,Wu, Chunying,Wang, Yanming
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p. 4902 - 4914
(2019/05/28)
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- Discovery of 1,2,3-Triazole Derivatives for Multimodality PET/CT/Cryoimaging of Myelination in the Central Nervous System
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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.
- Wu, Chunying,Eck, Brendan,Zhang, Sheng,Zhu, Junqing,Tiwari, Anand Dev,Zhang, Yifan,Zhu, Yunjie,Zhang, Jinming,Wang, Bin,Wang, Xizhen,Wang, Xu,You, Jingqiang,Wang, Jian,Guan, Yihui,Liu, Xingdang,Yu, Xin,Trapp, Bruce D.,Miller, Robert,Silver, Jerry,Wilson, David,Wang, Yanming
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p. 987 - 999
(2017/02/19)
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- RADIOLIGANDS FOR MYELIN
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A radioligand for labeling myelin includes a fluorescent trans-stilbene derivative.
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Paragraph 0095
(2017/10/06)
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- Convergent synthesis and properties of photoactivable NADPH mimics targeting nitric oxide synthases
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A new series of photoactivable NADPH mimics bearing one or two O-carboxymethyl groups on the adenosine moiety have been readily synthesized using click chemistry. These compounds display interesting one- or two-photon absorption properties. Their fluorescence emission wavelength and quantum yields (Φ) are dependent on the solvent polarity, with a red-shift in a more polar environment (λmax,em = 460-467 nm, Φ > 0.53 in DMSO, and λmax,em = 475-491 nm, Φ 0.17 in Tris). These compounds show good binding affinity towards the constitutive nNOS and eNOS, confirming for the first time that the carboxymethyl group can be used as a surrogate of phosphate. Two-photon fluorescence imaging of nanotriggers in living cells showed that the presence of one carboxymethyl group (especially on the 3′ position of the ribose) strongly favors the addressing of nanotriggers to eNOS in the cell context.
- Nguyen,Bogliotti,Chennoufi,Henry,Tauc,Salas,Roman,Slama-Schwok,Deprez,Xie
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p. 9519 - 9532
(2016/10/22)
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