ORCID Profile
0000-0002-7987-8160
Current Organisation
University of Oxford
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Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA04643F
Abstract: A cobalt tris(2-pyridylmethyl)amine complex cycles between stable paramagnetic Co( ii ) and diamagnetic Co( iii ) forms with corresponding changes in the MRI contrast.
Publisher: Ivyspring International Publisher
Date: 2023
DOI: 10.7150/THNO.82101
Publisher: Society of Nuclear Medicine
Date: 22-11-2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC07092J
Abstract: A novel, reversible redox-active MRI probe, GdNR1, has been developed based on the biologically-inspired nicotinimidium redox switch.
Publisher: Society of Nuclear Medicine
Date: 28-09-2023
Publisher: Wiley
Date: 02-05-2014
Publisher: American Chemical Society (ACS)
Date: 02-08-2017
DOI: 10.1021/ACS.INORGCHEM.7B01368
Abstract: Dense tumors are resistant to conventional chemotherapies due to the unique tumor microenvironment characterized by hypoxic regions that promote cellular dormancy. Bioreductive drugs that are activated in response to this hypoxic environment are an attractive strategy for therapy with anticipated lower harmful side effects in normoxic healthy tissue. Cobalt bioreductive pro-drugs that selectively release toxic payloads upon reduction in hypoxic cells have shown great promise as anticancer agents. However, the bioreductive response in the tumor microenvironment must be better understood, as current techniques for monitoring bioreduction to Co(II) such as X-ray absorption near-edge structure and extended X-ray absorption fine structure provide limited information on speciation and require synchrotron radiation sources. Here, we present magnetic resonance imaging (MRI) as an accessible and powerful technique to monitor bioreduction by treating the cobalt complex as an MRI contrast agent and monitoring the change in water signal induced by reduction from diamagnetic Co(III) to paramagnetic Co(II). Cobalt pro-drugs built upon the tris(2-pyridylmethyl)amine ligand scaffold with varying charge were investigated for distribution and activity in a 3D tumor spheroid model by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and MRI. In addition, paramagnetic
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7CC00619E
Abstract: A cobalt( ii ) complex can distinguish between anions by observing the paramagnetic 1 H NMR shift.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Springer Science and Business Media LLC
Date: 26-05-2022
DOI: 10.1007/S00259-022-05835-4
Abstract: 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 [ 18 F]rucaparib, an 18 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 [ 18 F]rucaparib in human pancreatic cancer models. We incorporated the positron-emitting 18 F isotope into rucaparib, enabling its use as a PET imaging agent. [ 18 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. Uptake of [ 18 F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [ 18 F]rucaparib. In vivo studies revealed relatively fast blood clearance of [ 18 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 [ 18 F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding. Taken together, we demonstrate the potential of [ 18 F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.NUCMEDBIO.2022.02.004
Abstract: Molecular radionuclide therapy (MRT) is an effective treatment for both localised and disseminated tumours. Biomarkers can be used to identify potential subtypes of tumours that are known to respond better to standard MRT protocols. These enrolment-based biomarkers can further be used to develop dose-response relationships using image-based dosimetry within these defined subtypes. However, the biological identity of the cancers treated with MRT are commonly not well-defined, particularly for neuroendocrine neoplasms. The biological heterogeneity of such cancers has hindered the establishment of dose-responses and minimum tumour dose thresholds. Biomarkers could also be used to determine normal tissue MRT dose limits and permit greater injected doses of MRT in patients. An alternative approach is to understand the repair capacity limits of tumours using radiobiology-based biomarkers within and outside patient cohorts currently treated with MRT. It is hoped that by knowing more about tumours and how they respond to MRT, biomarkers can provide needed dimensionality to image-based biodosimetry to improve MRT with optimized protocols and personalised therapies.
Publisher: Ivyspring International Publisher
Date: 2020
DOI: 10.7150/THNO.44772
Publisher: Society of Nuclear Medicine
Date: 09-10-2020
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
No related grants have been discovered for Edward O'Neill.