5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-y l)-1 H-indole as a potential PET radioligand for imaging cerebral I-7-nAChR in mice

The radiosynthesis and in vivo evaluation of 5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-y l )-1H-indole [11C]rac-(1), a potential PET tracer for I-7 nicotinic acetylcholine receptors (I-7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding de...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2012-06, Vol.20 (12), p.3698-3702
Main Authors: Gao, Yongjun, Ravert, Hayden T, Valentine, Heather, Scheffel, Ursula, Finley, Paige, Wong, Dean F, Dannals, Robert F, Horti, Andrew G
Format: Article
Language:English
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Summary:The radiosynthesis and in vivo evaluation of 5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-y l )-1H-indole [11C]rac-(1), a potential PET tracer for I-7 nicotinic acetylcholine receptors (I-7-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 [11C]CH3I afforded [11C]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/I14mol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [11C]rac-1 penetrates the bloodabrain barrier and specifically labels neuronal I-7-nAChRs.
ISSN:0968-0896
DOI:10.1016/j.bmc.2012.04.056