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Reports outline Alzheimer disease study findings from National Institute of Mental Health
2008 FEB 11 -- Researchers detail in 'Synthesis and evaluation of N-Methyl and S-Methyl 11C-Labeled 6-Methylthio-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridines as radioligands for imaging beta-amyloid plaques in Alzheimer's disease,' new data in Alzheimer disease. "6-Thiolato-substituted 2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridines (RS-IMPYs; 1-4) were synthesized as candidates for labeling with carbon-11 (t 1/2=20.4 min) and imaging of A beta plaques in living human brain using positron emission tomography (PET). K i values for binding of these ligands to Alzheimer's disease brain homogenates were measured in vitro against tritium-labeled 6 (Pittsburgh compound B)," researchers in the United States report. "MeS-IMPY (3, K i=7.93 nM) was labeled with carbon-11 at its S-or N-methyl position to give [ (11)C] 7 or [ (11)C] 8, respectively. After injection into rats, [ (11)C] 7 or [ (11)C] 8 gave moderately high brain uptakes of radioactivity followed by rapid washout to low levels. The ratio of radioactivity at maximal uptake to that at 60 min reached 18.7 for [ (11)C] 7. [ (11)C] 7 behaved similarly in mouse and monkey. [ (11)C] 7 also bound selectively to A beta plaques in post mortem human Alzheimer's disease brain. Although rapidly metabolized in rat by N-demethylation, [ (11)C] 7 was stable in rat brain homogenates. The ex vivo brain radiometabolites observed in rats have a peripheral origin," wrote L. Cai and colleagues, National Institute of Mental Health. The researchers concluded: "Overall, [ (11)C] 7 merits further evaluation in human subjects." Cai and colleagues published their study in the Journal of Medicinal Chemistry (Synthesis and evaluation of N-Methyl and S-Methyl 11C-Labeled 6-Methylthio-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridines as radioligands for imaging beta-amyloid plaques in Alzheimer's disease. Journal of Medicinal Chemistry, 2008;51(1):148-58). For additional information, contact L. Cai, National Institutes of Health, Molecular Imaging Branch and Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, Maryland 20892 USA.. Publisher contact information for the Journal of Medicinal Chemistry is: American Chemical Society, 1155 16th St., NW, Washington, DC 20036, USA. Keywords: United States, Bethesda, Alzheimer Disease, Medicinal Chemistry, Mental Health. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2008, Pain & Central Nervous System Week via NewsRx.com.
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