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Quantitative analyses of regional [11C]PE2I binding to the dopamine transporter in the human brain: a PET study.

Abstract：

PURPOSE:The dopamine transporter (DAT) is a plasma membrane protein of central interest in the pathophysiology of neuropsychiatric disorders and is known to be a target for psychostimulant drugs. [(11)C]PE2I is a new radioligand which binds selectively and with moderate affinity to central DAT, as has been demonstrated in vitro by autoradiography and in vivo by positron emission tomography (PET). The aims of the present PET study were to quantify regional [(11)C]PE2I binding to DAT in the human brain and to compare quantitative methods with regard to suitability for applied clinical studies. METHODS:One PET measurement was performed in each of eight healthy male subjects. The binding potential (BP) values were obtained by applying kinetic compartment analysis, which uses the metabolite-corrected arterial plasma curve as an input function. They were compared with the BP values quantified by two reference tissue approaches, using cerebellum as a reference region representing free and non-specific radioligand binding. RESULTS:The radioactivity concentration was highest in the striatum, lower in the midbrain and very low in the cerebellum. The regional [(11)C]PE2I binding could be interpreted by kinetic compartment models. However, the BP values in the striatum obtained by the compartment analyses were about 30% higher than the BP values obtained using reference tissue methods. We suggest that the difference may be explained by the inaccurate metabolite correction, small amounts of radioactive metabolites that could account for the presence of non-specific binding in the cerebellum and insufficient data acquisition time. CONCLUSION:The reference methods may be used to quantify [(11)C]PE2I binding in clinical studies, assuming that non-specific binding in the cerebellum does not vary between subjects and that an extended data acquisition time is employed. Moreover, the study corroborates the previous observation that [(11)C]PE2I is advantageous for PET examination of DAT binding in the midbrain, a region from which dopaminergic innervation originates and which is of central interest for the pathophysiology of several neuropsychiatric disorders.

journal_name

Eur J Nucl Med Mol Imaging

journal_title

European journal of nuclear medicine and molecular imaging

authors

Jucaite A,Odano I,Olsson H,Pauli S,Halldin C,Farde L

doi

10.1007/s00259-005-0027-9

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

657-68

issue

eissn

1619-7070

issn

1619-7089

journal_volume

pub_type

临床试验,杂志文章

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Quantitative analyses of regional [11C]PE2I binding to the dopamine transporter in the human brain: a PET study.