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Titolo:
Assessment of extrastriatal vesicular monoamine transporter binding site density using stereoisomers of [C-11]dihydrotetrabenazine
Autore:
Koeppe, RA; Frey, KA; Kuhl, DE; Kilbourn, MR;
Indirizzi:
Univ Michigan, Sch Med, Div Nucl Med, Dept Internal Med, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 nternal Med, Ann Arbor, MI 48109 USA
Titolo Testata:
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
fascicolo: 12, volume: 19, anno: 1999,
pagine: 1376 - 1384
SICI:
0271-678X(199912)19:12<1376:AOEVMT>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; OPIATE ANTAGONIST CYCLOFOXY; LIVING HUMAN-BRAIN; INACTIVE ENANTIOMERS; RECEPTOR-BINDING; KINETIC-ANALYSIS; C-11 DIHYDROTETRABENAZINE; RAT-BRAIN; PET; INVIVO;
Keywords:
[C-11]dihydrotetrabenazine; stereoisomers; tracer kinetics; monoamine vesicular transporter; vesicular monoamine transporter; positron emission tomography;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Koeppe, RA Univ Michigan, Sch Med, Div Nucl Med, Dept Internal Med, 3480 Kresge 3 Box0552, Ann Arbor, MI 48109 USA Univ Michigan 3480 Kresge 3 Box 0552 Ann Arbor MI USA 48109 USA
Citazione:
R.A. Koeppe et al., "Assessment of extrastriatal vesicular monoamine transporter binding site density using stereoisomers of [C-11]dihydrotetrabenazine", J CEREBR B, 19(12), 1999, pp. 1376-1384

Abstract

Previous studies have demonstrated the utility of [C-11]dihydrotetrabenazine ([C-11]DTBZ) as a ligand for in vivo imaging of the vesicular monoamine transporter system. The (+)-isomer has a high affinity (approximately 1 nmol/L) for the vesicular monoamine transporter (VMAT2) binding site, whereas the (-)-isomer has an extremely low affinity (approximately 2 mu mol/L). Efforts to model dynamic (+)-[C-11]DTBZ data demonstrate the difficulty in separating the specific binding component from the free plus nonspecific component of the total positron emission tomography (PET) measure. The authors'previous PET work, as well as in vitro studies, indicate that there is little specific VMAT2 binding in neocortical regions. However, precise determination of in vivo binding levels have not been made, leaving important questions unanswered. At one extreme, is there sufficient specific binding in cortex or other extrastriate regions to be estimated reliably with PET? At the other extreme, is there sufficiently little binding in cortex so that itcan be used as a reference region representing nonsaturable tracer uptake? The authors address these questions using paired studies with both active (+) and inactive (-) stereoisomers of [C-11]DTBZ. Six normal control subjects were scanned twice, 2 hours apart, after injections of 16 mCi of (+)- and (-)-[C-11]DTBZ (order counter-balanced). Three-dimensional PET acquisition consisted of 15 frames over 60 minutes for each scan. Arterial samples were acquired throughout, plasma counted, and corrected for radiolabeled metabolites. Analysis of specific binding was assessed by comparison of total distribution volume measures from the (+)- and (-)-[C-11]DTBZ scans. The authors' findings indicate that only approximately 540 of the cortical signal in (+)-[C-11]DTBZ scans result from binding to VMAT3 sites. The strongest extrastriatal signal comes from the midbrain regions where approximately 30%of the PET measure results from specific binding. The authors conclude that (1) the density of VMAT2 binding sites in cortical regions is not high enough to be quantified reliably with DTBZ PET, and (2) binding does appear to be low enough so that cortex can be used as a free plus nonspecific reference region for striatum.

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Documento generato il 24/09/20 alle ore 05:17:28