Journal article
Evaluation of a PET radioligand to image O-GlcNAcase in brain and periphery of rhesus monkey and knock-out mouse
S Paul, MB Haskali, JS Liow, SS Zoghbi, VN Barth, MC Kolodrubetz, MR Bond, CL Morse, RL Gladding, MP Frankland, N Kant, L Slieker, S Shcherbinin, HN Nuthall, P Zanotti-Fregonara, JA Hanover, C Jesudason, VW Pike, RB Innis
Journal of Nuclear Medicine | SOC NUCLEAR MEDICINE INC | Published : 2019
Abstract
Accumulation of hyperphosphorylated tau, a microtubule-associ-ated protein, plays an important role in the progression of Alzheimer disease. Animal studies suggest that one strategy for treating Alzheimer disease and related tauopathies may be inhibition of O-GlcNAcase (OGA), which may subsequently decrease pathologic tau phosphorylation. Here, we report the pharmacokinetics of a novel PET radioligand, 18 F-LSN3316612, which binds with high affinity and selectivity to OGA. Methods: PET imaging was performed on rhesus monkeys at baseline and after administration of either thiamet-G, a potent OGA inhibitor, or nonradioactive LSN3316612. The density of the enzyme was calculated as distribution ..
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Awarded by National Institute of Mental Health
Funding Acknowledgements
This work was supported by the Intramural Research Programs of NIDDK and NIMH (ZIAMH002793; ZIAMH002795) and a research grant from Eli Lilly & Co. Vanessa Barth, Nancy Kant, Lawrence Slieker, Sergey Shcherbinin, Hugh Nuthall, and Cynthia Jesudason were employees of Eli Lilly and Co. at the time the study was conducted. No other potential conflict of interest relevant to this article was reported.