The state-of-the art equipment called the Small Animal Radiation Research Platform (SARRP), manufactured by Xstrahl, will allow researchers to carry out more advanced, clinically relevant radiation experiments in preclinical models.
The need for enhanced radiation research
Radiotherapy - the use of high-energy radiation (usually X-rays) to kill cancer cells - is a cornerstone of cancer medicine used in the treatment of approximately 50% of cancer cases. It works by causing damage to the DNA of cancer cells, leading to cell death.
Radiotherapy is used to try to eradicate cancer, reduce the chance of cancer returning or to help relieve symptoms, and may be used on its own, or in combination with other cancer treatments, such as chemotherapy or surgery.
Although radiotherapy kills cancer cells, it can also damage healthy cells in the treatment area, leading to side effects. Cancer cells can also become resistant to the DNA-damaging effects of radiotherapy. Research to find ways to improve the efficacy of radiotherapy, reduce collateral damage to healthy cells, and limit the emergence of resistance, is vital to improve outcomes for patients.
Radiation research has become a priority for many funding bodies in the UK. In 2019, Cancer Research UK (CRUK) launched its £56 million radiation research network (CRUK RadNet), uniting seven centres across the UK to accelerate the development of advanced radiotherapy techniques. Queen Mary's BCI is a key partner in one of the CRUK RadNet centres – the CRUK RadNet City of London (CoL) Centre.
Accelerating radiation research in cancer and beyond
The installation of the SARRP represents a major upgrade to the radiation research infrastructure at Queen Mary that will benefit researchers across its FMD, and School of Engineering and Materials Science. With the new SARRP, research teams will be able to conduct computerised tomography (CT) image-guided radiotherapy in preclinical models that mimics clinical treatments to target tissue with high dose, accuracy and precision.
£490,000 of funding for the SARRP has been awarded from Queen Mary's Research Capital Investment Fund, which invests in key infrastructure projects to support areas of research excellence at the University. Barts Charity has awarded £50,000 towards the instrument costs.
A second project (Multi-modal Imaging-Guided Radiotherapy for small Animals with a Technological and Extensible System; MIGRATES), will enable magnetic resonance image (MRI)-guided radiotherapy to further maximise the capabilities of the SARRP. MIGRATES is funded by CRUK RadNet and is a collaboration within the RadNet Molecular Imaging and Radiotherapy Working Group.
At BCI, Dr Sosabowski and her team are working with CRUK RadNet CoL researchers (from University College London/Great Ormond Street Hospital and King's College London) to evaluate the effect of low dose radiation on the ability of tumour targeting T-cells (CAR-T cells) to infiltrate solid neuroblastoma tumours and overcome immune suppression.
These CAR-T cells are genetically modified to take up a radiotracer probe, which can be used to track the cells in live animals using single-photon emission computerized tomography (SPECT)/CT. Having both the SPECT imaging and radiotherapy instruments co-located at BCI allows investigation of these novel T-cell/radiotherapy combinations, making it possible to track the T-cells in the models over time.
Dr Sosabowski's team has also developed a computational 3D mouse atlas to identify pancreas and pancreatic tumours in MRI images of genetically modified mice. This ability to accurately locate pancreatic tumours will allow radiotherapy using the SARRP when combined with MRI imaging through the CRUK RadNet MIGRATES project.
Dr Sosabowski, Reader in Molecular Imaging and Lead Applicant for the Queen Mary funding award, said: "This new radiotherapy equipment at Queen Mary allows us to investigate exciting CAR-T cell/radiotherapy combinations for childhood cancers within our CRUK RadNet CoL Centre, and also to contribute to the CRUK-RadNet national network effort to develop multimodality image guided radiotherapy in experimental cancer models. We can use these tools to understand how radiation therapy can most effectively be used in patients."
Professor Hodivala-Dilke, Deputy Director of BCI and Queen Mary Lead for the CRUK RadNet CoL Centre, is working to improve the efficacy of radiotherapy in human solid cancers by understanding how non-cancerous cells within the tumour's environment, particularly those in the blood vessels, contribute to tumour growth and influence therapy efficacy.
Professor Hodivala-Dilke, who is Principal Investigator on the Barts Charity funding award and co-applicant for the Queen Mary funding award, said: "The new SARRP will allow some previously impossible experiments into understanding mechanisms of radiotherapy resistance that may have significant impact in future clinical radiotherapy strategies."
Other co-applicants on the Queen Mary funding award are Professor Silvia Marino from the Blizard Institute, Professor Philip Eaton from the William Harvey Research Institute and Professor Nikolaos Donos from the Institute of Dentistry.
Professor Marino's team will be using the SARRP to develop a mouse model of recurrent glioblastoma, the most common malignant brain tumour of the adult population and to study the effect of irradiation on the normal brain tissue at the margin of the tumour radiation field.
Not only will the SARRP accelerate Queen Mary's radiation research in cancer, but the platform will also allow researchers to explore the effects of radiation therapy in other biomedical fields. In the FMD's William Harvey Research Institute, Professor Philip Eaton is interested in the changes that occur in cardiac tissue following radiotherapy.
The new SARRP will allow Professor Eaton's team to study how the oxidative stress that occurs during cancer radiotherapy results in DNA changes that cause the heart to become scarred or 'fibrotic.' Fibrosis impairs cardiac function, and understanding the links between radiation and fibrosis will increase the likelihood of identifying drugs that limit this damage to the hearts of patients undergoing cancer radiotherapy.
In the Institute of Dentistry, Professor Donos' team will be building on previous preclinical studies in healthy and systemic disease related conditions working on models of wound healing after irradiation.
Vice-Principal (Research and Innovation) and Professor of Chemical Engineering Professor Andrew Livingston said: "The new SARRP is a significant step forward for Queen Mary and shows how we are investing in our research infrastructure so we can push the boundaries of what we can achieve through our research. I am excited to see the new opportunities this equipment will bring and the difference it will allow our researchers to make."
