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Titolo:
Carbon-11-NNC 112: A radioligand for PET examination of striatal and neocortical D-1-dopamine receptors
Autore:
Halldin, C; Foged, C; Chou, YH; Karlsson, P; Swahn, CG; Sandell, J; Sedvall, G; Farde, L;
Indirizzi:
Karolinska6Hosp, Dept Clin Neurosci, Psychiat Sect, Karolinska Inst, S-1717 Karolinska Hosp Stockholm Sweden S-17176 t Sect, Karolinska Inst, S-1717 Novo Nordisk AS, Malov, Denmark Novo Nordisk AS Malov DenmarkNovo Nordisk AS, Malov, Denmark
Titolo Testata:
JOURNAL OF NUCLEAR MEDICINE
fascicolo: 12, volume: 39, anno: 1998,
pagine: 2061 - 2068
SICI:
0161-5505(199812)39:12<2061:C1ARFP>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; DOPAMINE D1 RECEPTORS; C-11 METHYL TRIFLATE; SCH 23390; D2-DOPAMINE RECEPTORS; CEREBRAL-CORTEX; H-3 RACLOPRIDE; BINDING; NNC-687; NNC-756;
Keywords:
brain; D-1-dopamine receptors; striatal; neocortical; extrastriatal; NNC 112; carbon-11; PET;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Halldin, C Karolinska6Hosp, Dept Clin Neurosci, Psychiat Sect, Karolinska Inst, S-1717 Karolinska Hosp Stockholm Sweden S-17176 olinska Inst, S-1717
Citazione:
C. Halldin et al., "Carbon-11-NNC 112: A radioligand for PET examination of striatal and neocortical D-1-dopamine receptors", J NUCL MED, 39(12), 1998, pp. 2061-2068

Abstract

The aim of this work was to explore the potential of a selective D-1-dopamine receptor antagonist as a new radioligand for PET examination of striatal and neocortical D-1-dopamine receptors. Methods: The active (+)- and inactive (-)-enantiomers of [C-11]NNC 112 were radiolabeted using the N-methylation approach and were examined by PET in cynomolgus monkeys and healthy men. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography (HPLC). Results: N-methylation of the corresponding desmethyl precursors with [C-11]methyl triflate gave high total radiochemicalyield (50%-60%) and specific radioactivity (110 GBq/mu mol). (+)-[C-11]NNC112 binding in cynomolgus monkeys was 5.77 +/- 0.31 and 2.36 +/- 0.14 times higher in the striatum and neocortex, respectively, than in the cerebellum at a transient equilibrium that appeared 40-50 min after injection. The binding of (+)-[C-11]NNC 112 is stereoselective, because the brain distribution of the inactive (-)-enantiomer was on an equally low level for all brain regions, Displacement and pretreatment experiments using unlabeled SCH 23390 and ketanserin confirms that (+)-[C-11]NNC 112 binds specifically and reversibly to D-1-dopamine receptors. The radioactivity ratios of the striatum, frontal cortex and nucleus accumbens to the cerebellum were 3.8-4.0, 1.7-2.0 and 2.8-3.1, respectively, at a transient equilibrium that appeared 40-50 min after injection in four healthy human subjects. Linear graphical analysis gave distribution volume ratios of 3.9 and 1.5 in the putamen and frontal cortex, respectively, The fraction of the total radioactivity in human plasma representing unchanged (+)-[C-11]NNC 112 was 85% at 5 min and 25%at 75 min after injection. Conclusion: (+)-[C-11]NNC 112 should be a useful PET radioligand for quantitative examination of not only striatal but neocortical D-1-dopamine receptors in man.

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Documento generato il 20/01/20 alle ore 16:19:08