Linked Life Data

16934699

Source:http://linkedlifedata.com/resource/pubmed/id/16934699

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-8-28
pubmed:abstractText
The potent histamine H(3) receptor antagonist JNJ-10181457 (1) was successfully labeled with (11)C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28+/-8%) and high specific radioactivity (56+/-26 GBq/mumol). The binding of [(11)C]1 to H(3) receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [(11)C]1 in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H(3) antagonists, JNJ-5207852 (2) and unlabeled Compound (1), in a concentration-dependent manner. The biodistribution of [(11)C]1 in rats was measured at 5, 10, 30 and 60 min. The uptake of [(11)C]1 in regions rich in H(3) receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [(11)C]1 in the rat brain could not be blocked by pretreatment with either Compound (2) (30 min or 24 h pretreatment) or cold Compound (1) (30-min pretreatment). The biodistribution of [(11)C]1 in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H(3)(-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [(11)C]1 could not specifically label H(3) receptors in rodent brain in vivo. Possible causes are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0969-8051
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
801-10
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand.
pubmed:affiliation
Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article