Linked Life Data

15801845

Source:http://linkedlifedata.com/resource/pubmed/id/15801845

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-4-1
pubmed:abstractText
A series of new, fluorine-containing substituted diphenyl sulfides was synthesized to serve as candidate ligands for positron emission tomography (PET) imaging of the serotonin transporter (SERT) and to further probe the structure-activity relationship (SAR) of this class of compounds. Candidate compounds were assayed for their affinities to the monoamine transporters (SERT, norepinephrine transporter (NET), and dopamine transporter (DAT)) in competitive binding experiments in vitro using cloned human transporters. From these in vitro assays, four compounds (7c-f) were chosen for further evaluation. All four compounds have nanomolar affinity for SERT (K(i) 1.46 nM, 1.04 nM,1.83 nM, and 3.58 nM for 7c, 7d, 7e, and 7f, respectively). The F-18-labeled compounds, 16 and 18a-c, were prepared via a two-step radiosynthesis. Biodistribution studies in rats indicated that the F-18-labeled compounds localized in brain regions with high concentrations of SERT. Furthermore, competition experiments demonstrated that the binding of these radioligands in the rat brain was saturable, specific, and selective to SERT. Specific binding in the rat hypothalamus peaked at 5.6 for ligand 16 and 4.4 for 18b at 90 min after radioactivity administration. For ligand 18a, this same ratio was 8.4 at 120 min postinjection, while compound 18c displayed a lower specific binding ratio of 2.4. In summary, four F-18-labeled ligands were prepared and evaluated as candidate PET imaging agents for SERT. Among these four ligands, three appear to be promising radioligands suitable for the labeling of SERT in vivo, with 18a providing a higher specific binding in vivo than 16 or 18b.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2559-70
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15801845-Animals, pubmed-meshheading:15801845-Benzene Derivatives, pubmed-meshheading:15801845-Binding, Competitive, pubmed-meshheading:15801845-Brain, pubmed-meshheading:15801845-Cell Line, pubmed-meshheading:15801845-Fluorine Radioisotopes, pubmed-meshheading:15801845-Humans, pubmed-meshheading:15801845-Ligands, pubmed-meshheading:15801845-Male, pubmed-meshheading:15801845-Membrane Glycoproteins, pubmed-meshheading:15801845-Membrane Transport Proteins, pubmed-meshheading:15801845-Nerve Tissue Proteins, pubmed-meshheading:15801845-Positron-Emission Tomography, pubmed-meshheading:15801845-Radioligand Assay, pubmed-meshheading:15801845-Radiopharmaceuticals, pubmed-meshheading:15801845-Rats, pubmed-meshheading:15801845-Rats, Sprague-Dawley, pubmed-meshheading:15801845-Serotonin Plasma Membrane Transport Proteins, pubmed-meshheading:15801845-Structure-Activity Relationship, pubmed-meshheading:15801845-Sulfides, pubmed-meshheading:15801845-Tissue Distribution
pubmed:year
2005
pubmed:articleTitle
Fluorinated diaryl sulfides as serotonin transporter ligands: synthesis, structure-activity relationship study, and in vivo evaluation of fluorine-18-labeled compounds as PET imaging agents.
pubmed:affiliation
Department of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't