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)
|
Text
161141.pdf - Published Version Available under License Creative Commons Attribution. 2MB |
Abstract
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. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Pimlott, Dr Sally and Sutherland, Professor Andrew and Liuzzi, Maria Clara and Chalmers, Professor Anthony 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 > School 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: | 0022-2623 |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Altmetric
Altmetric