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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2008-8-7
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pubmed:abstractText |
Several isomers of 7-methyl-2-exo-([(18)F]fluoropyridinyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane have been developed as radioligands with optimized brain kinetics for PET imaging of nAChR. The binding assay demonstrated that all isomers are beta-nAChR selective ligands with Ki = 0.02-0.3 nM. The experimental lipophilicity values of all isomers were in the optimal range for the cerebral radioligands (log D7.4= 0.67-0.99). The isomers with higher binding affinity manifested slow baboon brain kinetics, whereas the isomer with the lowest binding affinity (Ki = 0.3 nM) ((-)-7-methyl-2- exo-[3'-(6-[(18)F]fluoropyridin-2-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane, [(18)F](-)-6c) and greatest lipophilicity (log D 7.4 = 0.99) exhibited optimal brain kinetics. [(18)F](-)-6c manifests a unique combination of the optimally rapid brain kinetics, high BP and brain uptake, and favorable metabolic profile. Pharmacological studies showed that (-)-6c is an alpha4beta2-nAChR antagonist with low side effects in mice. This combination of imaging properties suggests that [(18)F]-(-)- 6c is a potentially superior replacement for 2-[(18)F]fluoro-A-85380 and 6-[(18)F]fluoro-A-85380, the only available nAChR PET radioligands for humans.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:AlexanderMohabM,
pubmed-author:DannalsRobert FRF,
pubmed-author:GaoYongjunY,
pubmed-author:HiltonJohnJ,
pubmed-author:HortiAndrew GAG,
pubmed-author:KellarKennethK,
pubmed-author:KumarAnilA,
pubmed-author:KuwabaraHirotoH,
pubmed-author:RavertHayden THT,
pubmed-author:SpivakCharles ECE,
pubmed-author:WongDean FDF,
pubmed-author:XiaoYingxianY
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4751-64
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18605717-2,2'-Dipyridyl,
pubmed-meshheading:18605717-Animals,
pubmed-meshheading:18605717-Brain,
pubmed-meshheading:18605717-Cell Line,
pubmed-meshheading:18605717-Heptanes,
pubmed-meshheading:18605717-Humans,
pubmed-meshheading:18605717-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:18605717-Lipids,
pubmed-meshheading:18605717-Male,
pubmed-meshheading:18605717-Mice,
pubmed-meshheading:18605717-Molecular Structure,
pubmed-meshheading:18605717-Nicotinic Antagonists,
pubmed-meshheading:18605717-Papio,
pubmed-meshheading:18605717-Positron-Emission Tomography,
pubmed-meshheading:18605717-Radioligand Assay,
pubmed-meshheading:18605717-Rats,
pubmed-meshheading:18605717-Receptors, Nicotinic,
pubmed-meshheading:18605717-Stereoisomerism,
pubmed-meshheading:18605717-Structure-Activity Relationship,
pubmed-meshheading:18605717-Time Factors,
pubmed-meshheading:18605717-Tropanes
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pubmed:year |
2008
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pubmed:articleTitle |
Discovery of (-)-7-methyl-2-exo-[3'-(6-[18F]fluoropyridin-2-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane, a radiolabeled antagonist for cerebral nicotinic acetylcholine receptor (alpha4beta2-nAChR) with optimal positron emission tomography imaging properties.
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pubmed:affiliation |
Department of Radiology, Division of Nuclear Medicine, The Johns Hopkins UniVersity School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287-0816, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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