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DC Field | Value | Language |
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dc.contributor.author | Chan, CY | - |
dc.contributor.author | Chen, Z | - |
dc.contributor.author | Destro, G | - |
dc.contributor.author | Veal, M | - |
dc.contributor.author | Lau, D | - |
dc.contributor.author | O’Neill, E | - |
dc.contributor.author | Dias, G | - |
dc.contributor.author | Mosley, M | - |
dc.contributor.author | Kersemans, V | - |
dc.contributor.author | Guibbal, F | - |
dc.contributor.author | Gouverneur, V | - |
dc.contributor.author | Cornelissen, B | - |
dc.date.accessioned | 2024-07-25T15:55:46Z | - |
dc.date.available | 2024-07-25T15:55:46Z | - |
dc.date.issued | 2022-05-26 | - |
dc.identifier | ORCiD: Doreen Lau https://orcid.org/0000-0002-7623-2401 | - |
dc.identifier | ORCiD: Bart Cornelissen https://orcid.org/0000-0001-7581-3303 | - |
dc.identifier.citation | Chan, C.Y. et al. (2022) 'Imaging PARP with [<sup>18</sup>F]rucaparib in pancreatic cancer models', European Journal of Nuclear Medicine and Molecular Imaging, 49 (11), pp. 3668 - 3678. doi: 10.1007/s00259-022-05835-4. | en_US |
dc.identifier.issn | 1619-7070 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/29412 | - |
dc.description | Supplementary Information is available online at: https://link.springer.com/article/10.1007/s00259-022-05835-4#Sec18 . | en_US |
dc.description.abstract | Purpose: Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [<sup>18</sup>F]rucaparib, an <sup>18</sup>F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report the in vitro and in vivo evaluation of [<sup>18</sup>F]rucaparib in human pancreatic cancer models. Method: We incorporated the positron-emitting <sup>18</sup>F isotope into rucaparib, enabling its use as a PET imaging agent. [<sup>18</sup>F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models. Results: Uptake of [<sup>18</sup>F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [<sup>18</sup>F]rucaparib. In vivo studies revealed relatively fast blood clearance of [<sup>18</sup>F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration). In vitro and in vivo studies showed significant reduction of [<sup>18</sup>F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding. Conclusion: Taken together, we demonstrate the potential of [<sup>18</sup>F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers. | en_US |
dc.description.sponsorship | This research was supported by Cancer Research UK through the Oxford Institute for Radiation Oncology, Medical Research Council (MRC) (MR/R01695X/1, G.D. and F.G., and H3R00580, C.Y.C) and Pancreatic Cancer UK (PCUK H3R00510, C.Y.C). | en_US |
dc.format.extent | 3668 - 3678 | - |
dc.format.medium | Print-Electronic | - |
dc.language | English | - |
dc.language.iso | en | en_US |
dc.publisher | Springer Nature | en_US |
dc.rights | Copyright © The Author(s) 2022. Rights and permissions: Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/. | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | PARP | en_US |
dc.subject | Rucaparib | en_US |
dc.subject | [<sup>18</sup>F]Rucaparib | en_US |
dc.subject | PET imaging | en_US |
dc.subject | pancreatic cancer | en_US |
dc.title | Imaging PARP with [<sup>18</sup>F]rucaparib in pancreatic cancer models | en_US |
dc.title.alternative | Imaging PARP with [18F]rucaparib in pancreatic cancer models | en_US |
dc.type | Article | en_US |
dc.date.dateAccepted | 2022-05-08 | - |
dc.identifier.doi | https://doi.org/10.1007/s00259-022-05835-4 | - |
dc.relation.isPartOf | European Journal of Nuclear Medicine and Molecular Imaging | - |
pubs.issue | 11 | - |
pubs.publication-status | Published | - |
pubs.volume | 49 | - |
dc.identifier.eissn | 1619-7089 | - |
dc.rights.license | https://creativecommons.org/licenses/by/4.0/legalcode.en | - |
dc.rights.holder | The Author(s) | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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