Abstract
The radiosynthesis and in vivo evaluation of 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [(11)C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [(11)C]CH(3)I afforded [(11)C]rac-1 in an average radiochemical yield of 30 ± 5% (n=5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n=5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [(11)C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / diagnostic imaging*
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Brain / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Indoles* / antagonists & inhibitors
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Ligands
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Mice
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Mice, Inbred Strains
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Molecular Structure
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Positron-Emission Tomography*
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Pyridines* / antagonists & inhibitors
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Quinuclidines / pharmacology
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Radiopharmaceuticals* / antagonists & inhibitors
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Radiopharmaceuticals* / chemistry
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Receptors, Nicotinic / analysis*
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Receptors, Nicotinic / metabolism
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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5-(5-(6-((11)C)methyl-3,6-diazabicyclo(3.2.0)heptan-3-yl)pyridin-2-yl)-1H-indol
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Bridged Bicyclo Compounds, Heterocyclic
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Chrna7 protein, mouse
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Indoles
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Ligands
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N-(1-azabicyclo(2.2.2)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide
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Pyridines
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Quinuclidines
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Radiopharmaceuticals
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Receptors, Nicotinic
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alpha7 Nicotinic Acetylcholine Receptor