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Titolo:
KINETIC EVALUATION OF [C-11] DIHYDROTETRABENAZINE BY DYNAMIC PET - MEASUREMENT OF VESICULAR MONOAMINE TRANSPORTER
Autore:
KOEPPE RA; FREY KA; VANDERBORGHT TM; KARLAMANGLA A; JEWETT DM; LEE LC; KILBOURN MR; KUHL DE;
Indirizzi:
UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,DIV NUCL MED,3480 KRESGE 3,BOX 0552 ANN ARBOR MI 48109
Titolo Testata:
Journal of cerebral blood flow and metabolism
fascicolo: 6, volume: 16, anno: 1996,
pagine: 1288 - 1299
SICI:
0271-678X(1996)16:6<1288:KEO[DB>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; DOPA DECARBOXYLASE ACTIVITY; AMINO-ACID DECARBOXYLASE; CEREBRAL BLOOD-FLOW; HUMAN-BRAIN; PARKINSONS-DISEASE; IN-VIVO; BINDING; )H-3>DIHYDROTETRABENAZINE; DIHYDROTETRABENAZINE;
Keywords:
[C-11] DIHYDROTETRABENAZINE; TRACER KINETICS; 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:
42
Recensione:
Indirizzi per estratti:
Citazione:
R.A. Koeppe et al., "KINETIC EVALUATION OF [C-11] DIHYDROTETRABENAZINE BY DYNAMIC PET - MEASUREMENT OF VESICULAR MONOAMINE TRANSPORTER", Journal of cerebral blood flow and metabolism, 16(6), 1996, pp. 1288-1299

Abstract

(+)-alpha-[C-11]Dihydrotetrabenazine (DTBZ) binds to the vesicular monoamine transporter (VMAT2) located in presynaptic vesicles. The purpose of this work was to evaluate various model configurations for analysis of [C-11]DTBZ with the aim of providing the optimal measure of monoamine vesicular transporter density obtainable from a single dynamic PET study. PET studies on seven young normal volunteer subjects, ages 20-35, were performed following i.v. injection of 666 +/- 37 MBq (18 +/- 1 mCi) of (+)-alpha-[C-11]DTBZ. Dynamic acquisition consisted of a 15-frame sequence over 1 h. Analysis methods included both creation ofpixel-by-pixel functional images of transport (K-1) and binding (DVtot) and nonlinear least-squares analysis of volume-of-interest data. Pixel-by-pixel calculations were performed for both two-compartment weighted integral calculations and slope-intercept estimations from Logan plots. Nonlinear least-squares analysis was performed applying model configurations with both two-compartments, estimating K-1 and DVtot, and three compartments, estimating K-1-k(4). For the more complex configuration, we examined the stability of various binding-related parameters including k(3) (k(on)B(max)'), k(3)/k(4) (B-max'/K-d), DVsp [(K-1/k(2))(k(3)/k(4))], and DVtot [K-1/k(2)(1 + k(3)/k(4))]. The three-compartment model provided significantly improved goodness-of-fit compared to the two-compartment model, yet did not increase the uncertainty in the estimate of the DVtot. Without constraining parameters in the three-compartment model fits, DVtot was found to provide a more stable estimate of binding density than either k(3), k(3)/k(4), or DVsp. The two-compartment least-squares analysis yielded approximately 10% underestimations of the total distribution. However, this bias was found to bevery consistent from region to region as well as across subjects as indicated by the correlation between two- and three-compartment DVtot estimates of 0.997. We conclude that (+)-alpha-[C-11]DTBZ and PET can provide excellent measures of VMAT2 density in the human brain.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 17:10:13