Research article summary (published 29 Sep 2009):

In vitro autoradiography and in vivo evaluation in cynomolgus monkey of [18F]FE-PE2I, a new dopamine transporter PET radioligand.

Full Abstract

This study evaluated the in vitro and in vivo characteristics of a new dopamine transporter (DAT) radioligand, [(18)F]fluoroethyl(FE)PE2I, by autoradiography from postmortem human brain and by positron emission tomography (PET) in three cynomolgus monkeys. In the autoradiography experiments, high [18F]FE-PE2I accumulation was observed in caudate and putamen that was selectively abolished by GBR12909 or beta-CIT but not by maprotiline. High doses of citalopram (>5 microM) also inhibited [18F]FE-PE2I binding in the striatum. In vitro Ki of the radioligand was 12 nM at rodent dopamine transporter. [18F]FE-PE2I brain uptake measured by PET was approximately 4-5% of the injected dose, with highest uptake in striatum followed by midbrain and thalamus, lower uptake in neocortex, and lowest in cerebellum. Peak specific binding in striatum was reached approximately 40 min and in midbrain 20-30 min postinjection. The ratio-to-cerebellum was 7-10 in striatum and 1.5-2.3 in midbrain. BP(ND) measured with simplified reference tissue method using the cerebellum as reference region was 4.5 in striatum and 0.6 in midbrain. No displacement was shown after citalopram or maprotiline administration, while GBR12909 decreased the binding in striatum and midbrain to the level of cerebellum. [18F]FE-PE2I showed relatively fast elimination and metabolism with the presence of two metabolite peaks with similar retention time as the labeled metabolites of [11C]PE2I. [18F]FE-PE2I showed in vivo selectivity for the DAT and compared with [11C]PE2I, it showed faster kinetics and earlier peak equilibrium. The potential influence of the two radiometabolites on PET quantification requires further evaluation. Copyright 2009 Wiley-Liss, Inc.

Author information

Author/s: Varrone, Andrea (A); Steiger, Carsten (C); Schou, Magnus (M); Takano, Akihiro (A); Finnema, Sjoerd J (SJ); Guilloteau, Denis (D); Gulyás, Balázs (B); Halldin, Christer (C);

Affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden. andrea.varrone(-atsign-)ki.se

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't

Journal: Synapse (New York, N.Y.) (Synapse), published in United States. (Language: eng)

Reference: 2009-Oct; vol 63 (issue 10) : pp 871-80

Dates: Created 2009/08/11; Completed 2009/10/26;

PMID: 19562698, status: MEDLINE (last retrieved date: 10/26/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Autoradiography - methods Binding, Competitive - drug effects Brain - drug effects; metabolism; radionuclide imaging Citalopram - pharmacology Dopamine Plasma Membrane Transport Proteins - metabolism Dopamine Uptake Inhibitors - pharmacology Dose-Response Relationship, Drug Humans Macaca fascicularis

Macaca fascicularis Metabolic Clearance Rate Nortropanes - chemistry; metabolism Piperazines - pharmacology Positron-Emission Tomography - methods Postmortem Changes Protein Binding - drug effects; physiology Radiopharmaceuticals - metabolism Serotonin Uptake Inhibitors - pharmacology Tissue Distribution

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: (E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane (0) ; Dopamine Plasma Membrane Transport Proteins (0) ; Dopamine Uptake Inhibitors (0) ; Nortropanes (0) ; Piperazines (0) ; Radiopharmaceuticals (0) ; Serotonin Uptake Inhibitors (0) ; Citalopram (59729-33-8) ; vanoxerine (67469-78-7)

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