Source:http://linkedlifedata.com/resource/pubmed/id/15691664
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-2-4
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pubmed:abstractText |
[11C]N,N-Dimethyl-2-(2'-amino-4'-ethylphenylthio)benzylamine ([11C]EADAM) was synthesized in the development of a serotonin transporter (SERT) imaging ligand for positron emission tomography (PET). The methods of ligand synthesis, results of in vitro characterization, 11C labeling and in vivo micro-PET imaging studies of [11C]EADAM in cynomolgus monkey brain are described. 11C was introduced into N,N-dimethyl-2-(2'-amino-4'-ethylphenylthio)benzylamine (5) by alkylation of N-methyl-2-(2'-amino-4'-ethylphenylthio)benzylamine (10) in 32% radiochemical yield (end of bombardment [EOB], decay-corrected from [11C]methyl iodide). Competition binding assays in cells stably expressing the transfected human dopamine transporter (DAT), SERT and norepinephrine transporter (NET) labeled with [3H]WIN 35428 or [(125)I]RTI-55, [3H]citalopram and [3H]nisoxetine, respectively, indicated the following order of SERT affinity: ADAM>EADAM>>fluvoxamine. The affinity of EADAM for DAT and NET was 500- and >1000-fold lower, respectively, than for SERT. Micro-PET brain imaging studies in a cynomolgus monkey demonstrated high [11C]EADAM uptake in the striatum, thalamus and brainstem. [11C]EADAM uptake in these brain regions peaked in less than 60 min following administration of [11C]EADAM. The tissue-to-cerebellum ratios of the striatum, thalamus and brainstem were 1.67, 1.71 and 1.63, respectively, at 120 min postinjection of [11C]EADAM. Analysis of monkey arterial plasma samples using high-pressure liquid chromatography determined there was no detectable formation of lipophilic radiolabeled metabolites capable of entering the brain. In a displacement experiment with citalopram in a cynomolgus monkey, radioactivity in the striatum, thalamus and brainstem was displaced 20-60 min after administration of citalopram. In a blocking experiment with citalopram in a cynomolgus monkey, radioactivity in the striatum, thalamus and brainstem was significantly reduced. These results support the candidacy of [11C]EADAM as a radioligand for visualizing brain SERT using PET.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Carbon Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/N,N-dimethyl-2-(2-amino-4-methylphen...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Radiopharmaceuticals,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0969-8051
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pubmed:author |
pubmed-author:CampVernon MVM,
pubmed-author:GoodmanMark MMM,
pubmed-author:GoodmanRobin RRR,
pubmed-author:JarkasNachwaN,
pubmed-author:KiltsClinton DCD,
pubmed-author:MalveauxEugeneE,
pubmed-author:McConathyJonathanJ,
pubmed-author:VollRonald JRJ,
pubmed-author:VotawJohn RJR,
pubmed-author:WilliamsLarryL
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pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
75-86
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15691664-Animals,
pubmed-meshheading:15691664-Benzylamines,
pubmed-meshheading:15691664-Brain,
pubmed-meshheading:15691664-Carbon Radioisotopes,
pubmed-meshheading:15691664-Macaca fascicularis,
pubmed-meshheading:15691664-Male,
pubmed-meshheading:15691664-Membrane Glycoproteins,
pubmed-meshheading:15691664-Membrane Transport Proteins,
pubmed-meshheading:15691664-Metabolic Clearance Rate,
pubmed-meshheading:15691664-Nerve Tissue Proteins,
pubmed-meshheading:15691664-Positron-Emission Tomography,
pubmed-meshheading:15691664-Radiopharmaceuticals,
pubmed-meshheading:15691664-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:15691664-Tissue Distribution
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pubmed:year |
2005
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pubmed:articleTitle |
Synthesis and characterization of EADAM: a selective radioligand for mapping the brain serotonin transporters by positron emission tomography.
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pubmed:affiliation |
Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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