Synthesis and Evaluation of Eu(II/III) Systems for Imaging Transient Hypoxia

Lead Research Organisation: University of Oxford


The prolific nature of research into oxygen availability in the body is evident from the award of the Nobel Prize in Physiology or Medicine 2019. Hypoxia is where the body or a region of the body is oxygen deficient due to insufficient delivery of oxygen to living cells. It is significant because it is a major indicator of disease. Indeed, hypoxia is observed in various medical conditions such as Alzheimer's, cardiovascular diseases, kidney diseases, hepatic and neurological disorders, arthritis, metabolic diseases, diabetes, reproductive diseases, and cancer. In clinical medicine, there are currently no routine methods of detecting hypoxia, but clearly such technology, which essentially acts as a semi- universal indicator of disease, would be of significant benefit in improving healthcare.
Medical imaging is the process of generating an image of the interior of the body and the aim of this project is to make and evaluate chemical compounds, so-called imaging agents, that when administered to the patient enable imaging of hypoxia. The project will focus on europium-containing imaging agents because europium can form stable compounds in two oxidation states i.e. with a different charge on the europium ion, which are both accessible under physiological conditions and exhibit dramatically different magnetic properties and different properties in their interaction with light. This project is based on the hypothesis that the Eu2+ state should be favoured under hypoxic conditions, and the Eu3+ state under non-hypoxic conditions, hence leading to contrast in the generated image, enabling hypoxic tissue to be identified.
The ideal properties for a hypoxia sensing technique encompass excellent resolution in the image, non- invasiveness, no oxygen consumption, quantitative measurement of oxygen concentration, and negligible toxicity. Potential modes of imaging hypoxia include Magnetic Resonance Imaging (MRI) which is non-invasive and visualises morphological and functional anatomy with essentially unlimited depth penetration through use of strong magnetic fields and radiofrequency pulses. Utilising MRI would exploit the fact that one of the oxidation states of europium produces positive MRI contrast whereas the oxidation state does not. Another potential hypoxia imaging modality is optical imaging which is also non-invasive and is a powerful tool for visualising subcellular morphologies based on the use of molecules that absorb and emit light. Those that both absorb and emit light are so-called luminescent materials and are particularly useful for imaging as there are fewer chemical species in the body that exhibit luminescence than those that just absorb light, leading to a more defined image. Optical imaging with such europium-containing agents is also likely to produce good contrast because one of the oxidation states of europium displays longer lived luminescence than the other.
This project will begin with synthesis of various europium-containing imaging agents and characterisation of their chemical and physical properties and stability, followed by in vitro testing of the agents for MRI and optical imaging of hypoxia and finally in vivo testing of such imaging modalities.
This project falls within the EPSRC physical sciences and healthcare technologies research areas.

Planned Impact

The primary impact of the OxICFM CDT will be the highly-trained world-class scientists that it delivers. This impact will encompass both the short term (during their doctoral studies), the medium term (subsequent employment) and ultimately the longer timescale defined by their future careers and consequent impact on science, engineering and policy in the UK.

The impact of OxICFM students during their doctoral studies will be measured by the culture change in graduate training that the Centre brings about - in working at the interface between inorganic synthesis and manufacturing, and fostering cross-sector industry/academia working practices. By embedding not only from larger companies, but also SMEs, we have developed a training regime that has broader relevance across the sector, and the potential for building bridges by fostering new collaborations spanning enormous diversity in scientific focus and scale. Moreover, at a broader level, OxICFM offers to play a unique role as a major focus (and advocate) for manufacturing engagement with academic inorganic synthetic science in the UK.

From a scientific perspective, OxICFM will be uniquely able to offer a broad training programme incorporating innovative and challenging collaborative projects spanning all aspects of fundamental and applied inorganic synthesis, both molecular and materials based (40+ faculty). These will address key challenges in areas such as energy provision/storage, catalysis, and resource provision/renewal necessary to enhance the capability and durability of UK plc in the medium term. To give some idea of perspective, the output from previous CDTs in Oxford's MPLS Division include two start-up companies and in excess of 30 patents.

It is not only in the industrial and scientific realms that students will have impact during their timeframe of their doctorate. Part of the training programme will be in public engagement: team-based challenges in resource development/training and outreach exercises/implementation will form part of the annual summer school. These in turn will constitute a key part of the impact derived from the CDT by its engagement with the public - both face-to-face and through electronic/web-based media. As the centre matures, our aspiration is that our students - from diverse backgrounds - will act as ambassadors for the programme and promote even higher levels of inclusion from all parts of society.

For our partners, and businesses both large and small in the manufacturing sector, it will be our students who are considered the ultimate output of the OxICFM CDT. Our programme has been shaped by the need of such companies (frequently expressed in preliminary discussions) to recruit doctoral graduates who can apply themselves to a broad spectrum of multi-disciplinary challenges in manufacturing-related synthesis. OxICFM's cohort-based training programme integrates significant industry-led training components and has been designed to deliver a much broader skill set than standard PhD schemes. The current lack of CDT training at the interface of inorganic chemistry and manufacturing (and the relevance of inorganic molecules/materials to numerous industrial sectors) heightens the need for - and the potential impact of - the OxICFM CDT. Our students will represent a tangible and valuable asset to meet the long-term skills demand for scientists to develop new materials and nanotechnology identified in the UK Government's 2013 Foresight report.

In the longer term, the broad and relevant training delivered by OxICFM, and the uniquely wide perspective of the manufacturing sector it will deliver, will allow our graduates to obtain (and thrive in) positions of significant responsibility in industry and in research facilities/institutes. Ultimately we believe that many will go on to be future research leaders, driving innovation and changing research culture, and thereby making a lasting contribution to the UK economy.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023828/1 01/04/2019 30/09/2027
2714591 Studentship EP/S023828/1 01/10/2022 30/09/2026 Euan Sarson