Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Synthesis and In-Vivo Evaluation of [11C]p-PVP-MEMA as a PET Radioligand for Imaging Nicotinic Receptors

Frédéric Dollé A , Sandrine Langle A , Gaëlle Roger A , Roger R. Fulton B , Béatrice Lagnel-de Bruin A , David J. Henderson B , Françoise Hinnen A , Taliesha Paine C , Mark J. Coster D , Heric Valette A , Michel Bottlaender A and Michael Kassiou C E F G
+ Author Affliations
- Author Affliations

A CEA, Service Hospitalier Frédéric Joliot, Institut d’Imagerie Biomédicale, 4 Place du Général Leclerc, F-91401 Orsay, France.

B Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia.

C School of Chemistry, University of Sydney, NSW 2006, Australia.

D Eskitis Institute for Cell and Molecular Therapies, Griffith University, Don Young Rd, Nathan, Qld 4121, Australia.

E Discipline of Medical Radiation Sciences, University of Sydney, NSW 2006, Australia.

F Brain and Mind Research Institute, 100 Mallett St, Camperdown, NSW 2050, Australia.

G Corresponding author. Email: m.kassiou@usyd.edu.au

Australian Journal of Chemistry 61(6) 438-445 https://doi.org/10.1071/CH08083
Submitted: 27 February 2008  Accepted: 22 April 2008   Published: 19 June 2008

Abstract

Within the class of (4-pyridinyl)vinylpyridines developed by Abbott laboratories as potent neuronal nicotinic acetylcholine receptor ligands, p-PVP-MEMA ({(R)-2-[6-chloro-5-((E)-2-pyridin-4-ylvinyl)pyridin-3-yloxy]-1-methylethyl}methylamine) is the lead compound of a novel series that do not display the traditional nicotinic-like pyrrole-ring but still possessing high subnanomolar affinity (Ki 0.077 nm—displacement of [3H](–)cytisine from whole rat brain synaptic membranes). In the present study, p-PVP-MEMA and its nor-derivative ({(R)-2-[6-chloro-5-((E)-2-pyridin-4-ylvinyl)pyridin-3-yloxy]-1-methylethyl}methylamine) as precursor for labelling with the short-lived positron-emitter carbon-11 (T1/2 20.4 min) were synthesized in 10 chemical steps from 2-hydroxy-5-nitropyridine and Boc-d-alanine. N-Alkylation of nor-p-PVP-MEMA with [11C]methyl iodide afforded [11C]p-PVP-MEMA (>98% radiochemically pure, specific activity of 86.4 GBq μmol–1) in 2% (non-decay corrected and non-optimized) radiochemical yield, in 34 min (including HPLC purification and formulation). Preliminary positron emission tomography (PET) results obtained in a Papio hamadryas baboon showed that [11C]p-PVP-MEMA is not a suitable PET-radioligand.


Acknowledgements

The authors thank Dr Dirk Roeda for proofreading the manuscript. This work was supported by DEST and the French Embassy in Australia under the FAST program (FR040051).


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