A novel 18F-labelled high affinity agent for PET imaging of the translocator protein

Blair, A., Zmuda, F., Malviya, G., Chalmers, A. J. , Dewar, D. , Pimlott, S. L. and Sutherland, A. (2015) A novel 18F-labelled high affinity agent for PET imaging of the translocator protein. Chemical Science, 6(8), pp. 4772-4777. (doi: 10.1039/C5SC01647A)

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The translocator protein (TSPO) is an important target for imaging focal neuroinflammation in diseases such as brain cancer, stroke and neurodegeneration, but current tracers for non-invasive imaging of TSPO have important limitations. We present the synthesis and evaluation of a novel 3-fluoromethylquinoline-2-carboxamide, AB5186, which was prepared in eight steps using a one-pot two component indium(III)-catalysed reaction for the rapid and efficient assembly of the 4-phenylquinoline core. Biological assessment and the implementation of a physicochemical study showed AB5186 to have low nanomolar affinity for TSPO, as well as optimal plasma protein binding and membrane permeability properties. Generation of [18F]-AB5186 through 18F incorporation was achieved in good radiochemical yield and subsequent in vitro and ex vivo autoradiography revealed the ability of this compound to bind with specificity to TSPO in mouse glioblastoma xenografts. Initial positron emission tomography imaging of a glioma bearing mouse and a healthy baboon support the potential for [18F]-AB5186 use as a radiotracer for non-invasive TSPO imaging in vivo.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Pimlott, Dr Sally and Sutherland, Professor Andrew and Dewar, Dr Deborah and Chalmers, Professor Anthony and Malviya, Dr Gaurav
Authors: Blair, A., Zmuda, F., Malviya, G., Chalmers, A. J., Dewar, D., Pimlott, S. L., and Sutherland, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
College of Science and Engineering > School of Chemistry
Journal Name:Chemical Science
Publisher:Royal Society of Chemistry
ISSN (Online):2041-6539
Published Online:27 May 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Chemical Science 6(8):4772-4777
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
584861EPSRC Doctoral Training Grant 2011-2015Mary Beth KneafseyEngineering & Physical Sciences Research Council (EPSRC)EP/J500434/1VICE PRINCIPAL RESEARCH & ENTERPRISE
664561Sinapse Spirit FellowshipAndrew SutherlandSINAPSE (SINAPSE)UNSPECIFIEDCHEM - CHEMISTRY