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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1995-8-24
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pubmed:abstractText |
Mechanistic positron emission tomography (PET) studies using the deuterium isotope effect and specific pharmacological intervention were undertaken to examine the behavior of 6-[18F]fluorodopamine (6-[18F]-FDA; 1) and (-)-6-[18F]fluoronorepinephrine [(-)-6-[18F]FNE; 2] in the baboon heart. Two regiospecifically deuterated derivatives of 6-[18F]FDA [alpha,alpha-D2 (3) and beta,beta-D2 (4)] were used to assess the contributions of monoamine oxidase (MAO) and dopamine beta-hydroxylase, respectively, to the clearance kinetics of 6-[18F]FDA. Compound 3 showed a reduced rate of clearance, consistent with MAO-catalyzed cleavage of the alpha C-D bond, whereas compound 4 showed no change, indicating that cleavage of the beta C-D bond is not a rate-limiting step. Pretreatment with pargyline, an MAO inhibitor, also decreased the rate of clearance. Desipramine and tomoxetine [norepinephrine (NE) uptake inhibitors], but not GBR-12909 (a dopamine uptake inhibitor), blocked the uptake of both (-)-6-[18F]FNE and 6-[18F]FDA, with (-)-6-[18F]FNE showing a higher degree of blockade. Chiral HPLC demonstrated that 6-[18F]FDA is stereoselectively converted to (-)-6-[18F]FNE in vivo in the rat heart. These studies demonstrate that (a) the more rapid clearance of 6-[18F]FDA relative to (-)-6-[18F]FNE can be largely accounted for by metabolism by MAO; (b) selective deuterium substitution can be used to protect a radiotracer from metabolism in vivo and to favor a particular pathway; (c) 6-[18F]FDA and (-)-6-[18F]FNE share the NE transporter; (d) 6-[18F]FDA is stereoselectively converted to (-)-6-[18F]FNE in vivo; and (e) the profile of radioactivity in the heart for 6-[18F]FDA is complex, probably including labeled metabolites as well as neuronal and nonneuronal uptake.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/6-fluorodopamine,
http://linkedlifedata.com/resource/pubmed/chemical/6-fluoronorepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Desipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Deuterium,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Isotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Monoamine Oxidase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3042
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
682-90
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7616224-Animals,
pubmed-meshheading:7616224-Desipramine,
pubmed-meshheading:7616224-Deuterium,
pubmed-meshheading:7616224-Dopamine,
pubmed-meshheading:7616224-Fluorine Radioisotopes,
pubmed-meshheading:7616224-Heart,
pubmed-meshheading:7616224-Isotopes,
pubmed-meshheading:7616224-Monoamine Oxidase Inhibitors,
pubmed-meshheading:7616224-Myocardium,
pubmed-meshheading:7616224-Norepinephrine,
pubmed-meshheading:7616224-Papio,
pubmed-meshheading:7616224-Rats,
pubmed-meshheading:7616224-Tomography, Emission-Computed
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pubmed:year |
1995
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pubmed:articleTitle |
Mechanistic positron emission tomography studies of 6-[18F]fluorodopamine in living baboon heart: selective imaging and control of radiotracer metabolism using the deuterium isotope effect.
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pubmed:affiliation |
Department of Chemistry, Brookhaven National Laboratory, Upton, NY 11973, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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