An 18F-labeled poly(ADP-ribose) polymerase positron emission tomography imaging agent

Zmuda, F., Blair, A., Liuzzi, M. C., Malviya, G., Chalmers, A. J. , Lewis, D., Sutherland, A. and Pimlott, S. L. (2018) An 18F-labeled poly(ADP-ribose) polymerase positron emission tomography imaging agent. Journal of Medicinal Chemistry, 61(9), pp. 4103-4114. (doi: 10.1021/acs.jmedchem.8b00138) (PMID:29630818) (PMCID:PMC6007963)

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Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for positron emission tomography (PET) and single photon emission computed tomography imaging. Consequently, over the past decade, there has been a drive to develop nuclear imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based on the potent PARP inhibitor olaparib (1). Our lead PET tracer candidate, [18F]20, was synthesized and evaluated as a potential PARP PET radiotracer in mice bearing subcutaneous glioblastoma xenografts using ex vivo biodistribution and PET−magnetic resonance imaging techniques. Results showed that [18F]20 could be produced in a good radioactivity yield and exhibited specific PARP binding allowing visualization of tumors overexpressing PARP. [18F]20 is therefore a potential candidate radiotracer for in vivo PARP PET imaging.

Item Type:Articles
Keywords:Molecular medicine, drug discovery.
Glasgow Author(s) Enlighten ID:Pimlott, Dr Sally and Sutherland, Professor Andrew and Chalmers, Professor Anthony and Liuzzi, Maria Clara and Malviya, Dr Gaurav and Zmuda, Mr Filip
Authors: Zmuda, F., Blair, A., Liuzzi, M. C., Malviya, G., Chalmers, A. J., Lewis, D., Sutherland, A., and Pimlott, S. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Science and Engineering > School of Chemistry
Journal Name:Journal of Medicinal Chemistry
Publisher:American Chemical Society
ISSN (Online):1520-4804
Published Online:09 April 2018
Copyright Holders:Copyright © 2018 American Chemical Society
First Published:First published in Journal of Medicinal Chemistry 61(9):4103-4114
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 and Physical Sciences Research Council (EPSRC)EP/J500434/1VPO VICE PRINCIPAL RESEARCH & ENTERPRISE