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European Journal of Nuclear Medicine and Molecular Imaging

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01-09-2003 | Original Article

[¹¹C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

Authors: Christer Halldin, Nina Erixon-Lindroth, Stefan Pauli, Yuan-Hwa Chou, Yoshiro Okubo, Per Karlsson, Camilla Lundkvist, Hans Olsson, Denis Guilloteau, Patrick Emond, Lars Farde

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2003

Abstract

The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [¹¹C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [¹¹C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55–65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [¹¹C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40–50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [¹¹C]PE2I was 15–20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [¹¹C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man.

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Title: [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain
Authors: Christer Halldin
Nina Erixon-Lindroth
Stefan Pauli
Yuan-Hwa Chou
Yoshiro Okubo
Per Karlsson
Camilla Lundkvist
Hans Olsson
Denis Guilloteau
Patrick Emond
Lars Farde
Publication date: 01-09-2003
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2003
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-003-1212-3

At a glance: The STEP trials

Springer Medicine

[¹¹C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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