Please use this identifier to cite or link to this item:
http://dx.doi.org/10.25673/115216
Title: | Evaluation of thiadiazine-based PET radioligands for imaging the AMPA receptor |
Author(s): | Chen, Jiahui Ran, Wenqing Huang, Yiman Wei, Junjie Rong, Jian Wei, Huiyi Li, Yinlong Li, Guocong Chen, Zhen Collier, Lee Elghazawy, Nehal H. Sippl, Wolfgang ![]() Haider, Ahmed ![]() Liao, Kai Dong, Chenchen Li, Ying Xu, Hao He, Wenpeng Wang, Lu Liang, Steven H. |
Issue Date: | 2023 |
Type: | Article |
Language: | English |
Abstract: | As a subclass of ionotropic glutamate receptors (iGluRs), α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been implicated in various neurological disorders and neurodegenerative diseases. To further our understanding of AMPA receptor-related disorders in the central nervous system (CNS), it is important to be able to image and quantify AMPA receptors in vivo. In this study, we identified a novel F-containing AMPA positive allosteric modulator (PAM) 6 as a potential lead compound. Molecular docking studies and CNS PET multi-parameter optimization (MPO) analysis were used to predict the absorption, distribution, metabolism, and excretion (ADME) characteristics of 6 as a PET probe. The resulting PET probe, [18F]6 (codename [18F]AMPA-2109), was successfully radiolabeled and demonstrated excellent blood-brain barrier (BBB) permeability and high brain uptake in rodents and non-human primates. However, [18F]6 did not show substantial specific binding in the rodent or non-human primate brain. Further medicinal chemistry efforts are necessary to improve specific binding, and our work may serve as a starting point for the design of novel 18F-labeled AMPA receptor-targeted PET radioligands aimed for clinical translation. |
URI: | https://opendata.uni-halle.de//handle/1981185920/117172 http://dx.doi.org/10.25673/115216 |
Open Access: | ![]() |
License: | ![]() |
Journal Title: | Biomedicine & pharmacotherapy |
Publisher: | Elsevier Science |
Publisher Place: | Amsterdam [u.a.] |
Volume: | 168 |
Original Publication: | 10.1016/j.biopha.2023.115842 |
Appears in Collections: | Open Access Publikationen der MLU |
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1-s2.0-S0753332223016402-main.pdf | 6.4 MB | Adobe PDF | ![]() View/Open |