Zmuda, F., Malviya, G. , Blair, A., Boyd, M., Chalmers, A. J. , Sutherland, A. and Pimlott, S. L. (2015) Synthesis and evaluation of a radioiodinated tracer with specificity for poly(ADP-ribose) polymerase-1 (PARP-1) in vivo. Journal of Medicinal Chemistry, 58(21), pp. 8683-8693. (doi: 10.1021/acs.jmedchem.5b01324) (PMID:26469301)
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Abstract
Interest in nuclear imaging of poly(ADP-ribose) polymerase-1 (PARP-1) has grown in recent years due to the ability of PARP-1 to act as a biomarker for glioblastoma and increased clinical use of PARP-1 inhibitors. This study reports the identification of a lead iodinated analog 5 of the clinical PARP-1 inhibitor olaparib as a potential single-photon emission computed tomography (SPECT) imaging agent. Compound 5 was shown to be a potent PARP-1 inhibitor in cell-free and cellular assays, and it exhibited mouse plasma stability but approximately 3-fold greater intrinsic clearance when compared to olaparib. An 123I-labeled version of 5 was generated using solid state halogen exchange methodology. Ex vivo biodistribution studies of [123I]5 in mice bearing subcutaneous glioblastoma xenografts revealed that the tracer had the ability to be retained in tumor tissue and bind to PARP-1 with specificity. These findings support further investigations of [123I]5 as a noninvasive PARP-1 SPECT imaging agent.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Pimlott, Dr Sally and Malviya, Dr Gaurav and Sutherland, Professor Andrew and Chalmers, Professor Anthony and Boyd, Dr Marie |
| Authors: | Zmuda, F., Malviya, G., Blair, A., Boyd, M., Chalmers, A. J., 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 |
| Journal Name: | Journal of Medicinal Chemistry |
| Publisher: | American Chemical Society |
| ISSN: | 0022-2623 |
| ISSN (Online): | 1520-4804 |
| Copyright Holders: | Copyright © 2015 American Chemical Society |
| First Published: | First published in Journal of Medicinal Chemistry 58(21):8683-8693 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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