Source:http://linkedlifedata.com/resource/pubmed/id/12126044
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2002-7-19
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pubmed:abstractText |
5-Iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA), an A-85380 analog iodinated at the 5-position of the pyridine ring, was evaluated as a radiopharmaceutical for investigating brain nicotinic acethylcholine receptors (nAChRs) by single photon emission computed tomography (SPECT). [123/125I]5IA was synthesized by the iododestannylation reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC) with high radiochemical yield (50%), high radiochemical purity (> 98%), and high specific radioactivity (> 55 GBq/micromol). The binding affinity of 5IA for brain nAChRs was measured in terms of displacement of [3H]cytisine and [125I]5IA from binding sites in rat cortical membranes. The binding data revealed that the affinity of 5IA was the same as that of A-85380 and more than seven fold higher than that of (-)-nicotine, and that 5IA bound selectively to the alpha4beta2 nAChR subtype. Biodistribution studies in rats indicated that the brain uptake of [125I]51A was rapid and profound. Regional cerebral distribution studies in rats demonstrated that the accumulation of [125I]5IA was consistent with the density of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus, moderate uptake in the cortex and lowest uptake in the cerebellum. Administration of the nAChR agonists (-)-cytisine and (-)-nicotine reduced the uptake of [125I]5IA in all regions studied with most pronounced reduction in the thalamus, and resulted in similar levels of radioactivity throughout the brain. [125I]5IA binding sites were shown to be saturable with unlabeled 5IA. Behavioral studies in mice demonstrated that 5IA did not show signs of behavioral toxicity. Furthermore, SPECT studies with [123I]5IA in the common marmoset demonstrated appropriate brain uptake and regional localization for a high-affinity nAChR imaging radiopharmaceutical. These results suggested that [123I]5IA is a promising radiopharmaceutical for SPECT studies of central nAChRs in human subjects.
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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/5-iodo-3-(2-azetidinylmethoxy)pyridi...,
http://linkedlifedata.com/resource/pubmed/chemical/Azetidines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Radiopharmaceuticals,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0914-7187
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pubmed:author |
pubmed-author:IidaYasuhikoY,
pubmed-author:KawashimaHidekazuH,
pubmed-author:KitamuraYoujiY,
pubmed-author:KiyonoYasushiY,
pubmed-author:MagataYasuhiroY,
pubmed-author:MukaiTakahiroT,
pubmed-author:NakagawaMasakiM,
pubmed-author:OgawaMikakoM,
pubmed-author:SajiHideoH,
pubmed-author:TominagaAkikoA,
pubmed-author:UedaMasashiM
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pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
189-200
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12126044-Animals,
pubmed-meshheading:12126044-Azetidines,
pubmed-meshheading:12126044-Brain,
pubmed-meshheading:12126044-Callithrix,
pubmed-meshheading:12126044-Male,
pubmed-meshheading:12126044-Mice,
pubmed-meshheading:12126044-Mice, Inbred ICR,
pubmed-meshheading:12126044-Pyridines,
pubmed-meshheading:12126044-Radiopharmaceuticals,
pubmed-meshheading:12126044-Rats,
pubmed-meshheading:12126044-Rats, Inbred BB,
pubmed-meshheading:12126044-Receptors, Nicotinic,
pubmed-meshheading:12126044-Reproducibility of Results,
pubmed-meshheading:12126044-Sensitivity and Specificity,
pubmed-meshheading:12126044-Tissue Distribution,
pubmed-meshheading:12126044-Tomography, Emission-Computed, Single-Photon,
pubmed-meshheading:12126044-Whole-Body Counting
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pubmed:year |
2002
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pubmed:articleTitle |
Evaluation of radioiodinated 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine as a ligand for SPECT investigations of brain nicotinic acetylcholine receptors.
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pubmed:affiliation |
Graduate School of Pharmaceutical Sciences, Kyoto University, Japan. hsaji@pharm.kyoto-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Evaluation Studies
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