Linked Life Data

10994724

Source:http://linkedlifedata.com/resource/pubmed/id/10994724

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-10-5
pubmed:abstractText
Abnormal brain regional densities of serotonin (5-hydroxytryptamine [5-HT]) transporters have been reported in postmortem studies in several neuropsychiatric conditions, such as major depression and schizophrenia. trans-1,2,3,5,6,10-beta-Hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline ([11C]McN 5652) is the first PET radioligand successfully developed to label 5-HT transporters in the living human brain. The purpose of this study was to develop an imaging protocol and analytic method to measure regional 5-HT transporter binding potential (BP) with [11C]McN 5652 in humans. METHODS: The arterial input function and brain uptake of (+)-[11C]McN 5652 and (-)-[11C]McN 5652, the active and inactive enantiomers, respectively, were measured in 6 healthy volunteers. Results: (+)-[11C]McN 5652 concentrated in brain regions rich in 5-HT transporters (midbrain, thalamus, basal ganglia, and medial temporal lobe structures), whereas the uptake of (-)-[11C]McN 5652 was more uniformly distributed. Total distribution volumes (V(T)) were derived using kinetic 2-compartment analysis and graphic analysis. V(T) derived by both methods were highly correlated. (+)-[11C]McN 5652 regional V(T) ranged from 18 +/- 2 mL/g in the cerebellum to 46 +/- 13 mL/g in the midbrain. (-)-[11C]McN 5652 regional VT ranged from 10 +/- 2 mL/g in the cerebellum to 14 +/- 3 mL/g in the thalamus. (+)-[11C]McN 5652 V(T) were higher than (-)-[11C]McN 5652 V(T) in all regions, including the cerebellum, a region devoid of 5-HT transporters. Blocking experiments were also performed in baboons with saturating doses of citalopram and in humans with nonsaturating doses of paroxetine. Cerebellar and neocortical (+)-[11C]McN 5652 V(T) were unaffected by pretreatment with 5-HT transporter blockers. In areas of high receptor concentration (midbrain, caudate, and thalamus) 5-HT transporter blockers decreased (+)-[11C]McN 5652 V(T) to the level of cerebellum (+)-[11C]McN 5652 V(T). CONCLUSION: These experiments indicate that the use of the difference between (+)- and (-)-[11C]McN 5652 V(T) to define specific binding to 5-HT transporters leads to an overestimation of specific binding. 5-HT transporter BP was derived as the difference between the regional and cerebellar (+)-[11C]McN 5652 V(T). BP values were in good agreement with the distribution of 5-HT transporters in the human brain, except for regions of relatively low 5-HT transporter concentration, such as the prefrontal cortex, where no specific binding was detected using (+)-[11C]McN 5652. (+)-[11C]McN 5652 is an appropriate radiotracer to quantify 5-HT transporters in regions with relatively high concentration of 5-HT transporters, such as the midbrain, thalamus, and basal ganglia, and should prove useful in elucidating abnormalities of 5-HT transmission in neuropsychiatric conditions.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0161-5505
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1465-77
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10994724-Adult, pubmed-meshheading:10994724-Brain, pubmed-meshheading:10994724-Carrier Proteins, pubmed-meshheading:10994724-Humans, pubmed-meshheading:10994724-Iodine Radioisotopes, pubmed-meshheading:10994724-Isoquinolines, pubmed-meshheading:10994724-Kinetics, pubmed-meshheading:10994724-Magnetic Resonance Imaging, pubmed-meshheading:10994724-Male, pubmed-meshheading:10994724-Membrane Glycoproteins, pubmed-meshheading:10994724-Membrane Transport Proteins, pubmed-meshheading:10994724-Mesencephalon, pubmed-meshheading:10994724-Nerve Tissue Proteins, pubmed-meshheading:10994724-Reference Values, pubmed-meshheading:10994724-Serotonin Antagonists, pubmed-meshheading:10994724-Serotonin Plasma Membrane Transport Proteins, pubmed-meshheading:10994724-Tissue Distribution, pubmed-meshheading:10994724-Tomography, Emission-Computed
pubmed:year
2000
pubmed:articleTitle
In vivo quantification of brain serotonin transporters in humans using [11C]McN 5652.
pubmed:affiliation
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.