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rdf:type |
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lifeskim:mentions |
umls-concept:C0011923,
umls-concept:C0031268,
umls-concept:C0032743,
umls-concept:C0184511,
umls-concept:C0220781,
umls-concept:C0220825,
umls-concept:C0242643,
umls-concept:C0542341,
umls-concept:C0597354,
umls-concept:C0963621,
umls-concept:C1883254
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pubmed:issue |
19
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pubmed:dateCreated |
2008-10-2
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pubmed:abstractText |
[(11)C]Loperamide has been proposed for imaging P-glycoprotein (P-gp) function with positron emission tomography (PET), but its metabolism to [N-methyl-(11)C] N-desmethyl-loperamide ([(11)C]dLop; [(11)C]3) precludes quantification. We considered that [(11)C]3 might itself be a superior radiotracer for imaging brain P-gp function and therefore aimed to prepare [(11)C]3 and characterize its efficacy. An amide precursor (2) was synthesized and methylated with [(11)C]iodomethane to give [(11)C]3. After administration of [(11)C]3 to wild-type mice, brain radioactivity uptake was very low. In P-gp (mdr-1a(-/-)) knockout mice, brain uptake of radioactivity at 30 min increased about 3.5-fold by PET measures, and over 7-fold by ex vivo measures. In knockout mice, brain radioactivity was predominantly (90%) unchanged radiotracer. In monkey PET experiments, brain radioactivity uptake was also very low but after P-gp blockade increased more than 7-fold. [(11)C]3 is an effective new radiotracer for imaging brain P-gp function and, in favor of future successful quantification, appears free of extensive brain-penetrant radiometabolites.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-10716325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-11181832,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-11902585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-12360104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-12455064,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-12902425,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-14667492,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-15319335,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-15668963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-15750163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-15912274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-15967124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-16239972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-16513622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-16954549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-17117422,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-17268016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-18067245,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-18344435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-1974900,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-22440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-2833666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-4725924,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-476289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-7910522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-8508715,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-8647944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-8790221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-9021112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18783208-9435299
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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 |
Oct
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
9
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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 |
6034-43
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18783208-Animals,
pubmed-meshheading:18783208-Brain,
pubmed-meshheading:18783208-Carbon Radioisotopes,
pubmed-meshheading:18783208-Injections, Intravenous,
pubmed-meshheading:18783208-Loperamide,
pubmed-meshheading:18783208-Macaca mulatta,
pubmed-meshheading:18783208-Male,
pubmed-meshheading:18783208-Mice,
pubmed-meshheading:18783208-Mice, Knockout,
pubmed-meshheading:18783208-Molecular Structure,
pubmed-meshheading:18783208-P-Glycoproteins,
pubmed-meshheading:18783208-Positron-Emission Tomography,
pubmed-meshheading:18783208-Radiopharmaceuticals,
pubmed-meshheading:18783208-Stereoisomerism,
pubmed-meshheading:18783208-Time Factors
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pubmed:year |
2008
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pubmed:articleTitle |
Synthesis and evaluation of [N-methyl-11C]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function.
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pubmed:affiliation |
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1103, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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