Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-3-6
pubmed:abstractText
2beta-Carbomethoxy-3beta-(4'-((Z)-2-iodoethenyl)phenyl)nortropane (ZIENT) (6) and 2beta-carbomethoxy-3beta-(4'-((E)-2-iodoethenyl)phenyl)nortropane (EIENT) (10) were prepared and evaluated in vitro and in vivo for serotonin transporter (SERT) selectivity and specificity. High specific activity [(123)I]ZIENT and [(123)I]EIENT were synthesized in 45% (n = 5) and 42% (n = 4) radiochemical yield (decay-corrected to end of bombardment (EOB)), respectively, by preparation of the precursor carbomethoxy-3beta-(4'-((Z)-2-trimethylstannylethenyl)phenyl)nortropane (7) and 2beta-carbomethoxy-3beta-(4'-((E)-2-tributylstannylethenyl)phenyl)nortropane (9), respectively, followed by treatment with no carrier-added sodium [(123)I]iodide and hydrogen peroxide in ethanolic HCl. Competition binding in cells stably expressing the transfected human SERT, dopamine transporter (DAT), and norepinephrine transporter (NET) using [(3)H]citalopram, [(3)H]WIN 35,428, and [(3)H]nisoxetine, respectively, demonstrated the following order of SERT affinity (K(i) in nM): ZIENT (0.05) > nor-CIT (0.12) >> EIENT (1.15) > fluvoxamine (1.46). The affinity of ZIENT and EIENT for DAT was 69 and 1.6-fold lower, respectively, than for SERT. In vivo biodistribution and blocking studies were performed in male rats and demonstrated that the brain uptake of [(123)I]ZIENT was selective and specific for SERT-rich regions (hypothalamus, striatum, pons, and prefrontal cortex). SPECT brain imaging studies in monkeys demonstrated high [(123)I]ZIENT uptake in the diencephalon, which resulted in diencephalon-to-cerebellum ratios of 2.12 at 190 min. [(123)I]ZIENT uptake in the diencephalon achieved transient equilibrium at 157 min. In a displacement experiment of [(123)I]ZIENT in a cynomolgus monkey, radioactivity was reduced by 39% in the diencephalon at 101 min following injection of citalopram. The high specific activity one-step radiolabeling preparation and high selectivity of [(123)I]ZIENT for SERT support its candidacy as a radioligand for mapping brain SERT sites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes, http://linkedlifedata.com/resource/pubmed/chemical/Ligands, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nortropanes, http://linkedlifedata.com/resource/pubmed/chemical/Radiopharmaceuticals, http://linkedlifedata.com/resource/pubmed/chemical/SLC6A4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane..., http://linkedlifedata.com/resource/pubmed/chemical/Slc6a4 protein, rat
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
925-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12620070-Animals, pubmed-meshheading:12620070-Binding, Competitive, pubmed-meshheading:12620070-Brain, pubmed-meshheading:12620070-Carrier Proteins, pubmed-meshheading:12620070-Female, pubmed-meshheading:12620070-HeLa Cells, pubmed-meshheading:12620070-Humans, pubmed-meshheading:12620070-Iodine Radioisotopes, pubmed-meshheading:12620070-Isotope Labeling, pubmed-meshheading:12620070-Ligands, pubmed-meshheading:12620070-Macaca fascicularis, pubmed-meshheading:12620070-Male, pubmed-meshheading:12620070-Membrane Glycoproteins, pubmed-meshheading:12620070-Membrane Transport Proteins, pubmed-meshheading:12620070-Nerve Tissue Proteins, pubmed-meshheading:12620070-Nortropanes, pubmed-meshheading:12620070-Radioligand Assay, pubmed-meshheading:12620070-Radiopharmaceuticals, pubmed-meshheading:12620070-Rats, pubmed-meshheading:12620070-Rats, Sprague-Dawley, pubmed-meshheading:12620070-Serotonin, pubmed-meshheading:12620070-Serotonin Plasma Membrane Transport Proteins, pubmed-meshheading:12620070-Stereoisomerism, pubmed-meshheading:12620070-Structure-Activity Relationship, pubmed-meshheading:12620070-Tissue Distribution, pubmed-meshheading:12620070-Tomography, Emission-Computed, Single-Photon
pubmed:year
2003
pubmed:articleTitle
Synthesis and characterization of iodine-123 labeled 2beta-carbomethoxy-3beta-(4'-((Z)-2-iodoethenyl)phenyl)nortropane. A ligand for in vivo imaging of serotonin transporters by single-photon-emission tomography.
pubmed:affiliation
Department of Radiology, Emory University, Atlanta, Georgia 30320, USA. mgoodma@emory.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't