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Titolo:
EQUILIBRIUM VERSUS COMPARTMENTAL ANALYSIS FOR ASSESSMENT OF THE VESICULAR MONOAMINE TRANSPORTER USING (-ALPHA-[C-11]DIHYDROTETRABENAZINE (DTBZ) AND POSITRON-EMISSION-TOMOGRAPHY())
Autore:
KOEPPE RA; FREY KA; KUME A; ALBIN R; KILBOURN MR; KUHL DE;
Indirizzi:
UNIV MICHIGAN,SCH MED,DIV NUCL MED,DEPT INTERNAL MED,3480 KRESGE 3 BOX 0552 ANN ARBOR MI 48109 UNIV MICHIGAN,DEPT NEUROL ANN ARBOR MI 48109 ANN ARBOR VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN ANN ARBOR MI 00000
Titolo Testata:
Journal of cerebral blood flow and metabolism
fascicolo: 9, volume: 17, anno: 1997,
pagine: 919 - 931
SICI:
0271-678X(1997)17:9<919:EVCAFA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-BRAIN; BENZODIAZEPINE RECEPTORS; BINDING; PET; DIHYDROTETRABENAZINE; LIGAND; RAT;
Keywords:
(+)-ALPHA-[C-11]DIHYDROTETRABENAZINE; TRACER KINETICS; EQUILIBRIUM ANALYSIS; VMAT2; MONOAMINE VESICULAR TRANSPORTER; POSITRON EMISSION TOMOGRAPHY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
R.A. Koeppe et al., "EQUILIBRIUM VERSUS COMPARTMENTAL ANALYSIS FOR ASSESSMENT OF THE VESICULAR MONOAMINE TRANSPORTER USING (-ALPHA-[C-11]DIHYDROTETRABENAZINE (DTBZ) AND POSITRON-EMISSION-TOMOGRAPHY())", Journal of cerebral blood flow and metabolism, 17(9), 1997, pp. 919-931

Abstract

This work compares equilibrium to kinetic analysis of positron emission tomography data for the assessment of vesicular monoamine transporter (VMAT2) binding density using (+)-alpha-[C-11]dihydrotetrabenazine ((+)-alpha-[C-11]DTBZ). Studies were performed for 80 minutes after intravenous administration of 18 +/- 1 mCi (+)-alpha-[C-11]DTBZ on 9 young control subjects, 20 to 45 years of age. A 9-mCi bolus was injectedover the first minute of the study, whereas the remaining 9 mCi were infused at a constant rate over the following 79 minutes. Steady-statewas reached in both blood and brain by approximately 30 minutes afterinitiation of the study. Nonlinear least-squares analysis using two-and three-compartment models, weighted integral analysis using a two-compartment configuration, and Logan plot analysis all yielded kinetic estimates of the total tissue distribution volume, DVtot(kin). These results were compared with equilibrium distribution volume estimates, DVtot(eq), calculated from the tissue to metabolite corrected arterial plasma concentration ratio after 30 minutes. Kinetic modeling results from this study were in close agreement with prior bolus-injection (+)-alpha-[C-11]DTBZ studies. In the current study, coefficients of variation in DVtot(kin) (19% to 23% across regions) and DVtot(eq) (18% to 22%) were nearly identical. Equilibrium estimates of DVtot(eq) were slightly lower than kinetic estimates, averaging 5% +/- 9% lower (P = 0.04, paired t test) in regions of high binding density (caudate and putamen), but only 2% +/- 6% (P = 0.09) in lower binding density regions (cortex, thalamus, cerebellum). DVtot(eq) estimates, however, still correlated highly with DVtot(kin) estimates (r = 0.977 - 0.989). Steady-state conditions can be achieved in both tissue and blood by 30 minutes,and the tissue-to-blood ratios of (+)-alpha-[C-11]DTBZ at equilibriumyield DVtot(eq) measures that are in close agreement with DVtot(kin) estimates. Thus, a simple, easily tolerated protocol using a loading bolus followed by continuous infusion can provide excellent measures ofVMAT2 binding.

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Documento generato il 18/09/20 alle ore 17:14:00