Physical and biological characterisation of clinically relevant combined MRI-radiation exposures with conventional and nanoparticle contrast agents

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Magnetic resonance imaging (MRI) is used throughout radiotherapy due to excellent soft tissue contrast aiding delineationof the tumour in a variety of treatment sites. MRI is generally considered a safe technology with very high clinical impact. Itis accepted as a powerful non-invasive diagnostic tool to investigate the anatomical structures and functions in the body, inboth health and disease. It is estimated that 200 million MRI scans have been performed worldwide and no direct adversebiological effects have been reported in subjects/patients. Radiotherapy is a highly effective treatment for a wide number ofdisease sites and plays a major role in 50% of all cancer treatments. Recent technological advances have allowedtreatments which conform better to the tumour while avoiding normal tissue. This improved conformity often requiresimproved image guided radiotherapy (IGRT) generally performed using cone beam CT (CBCT) scans taken directly pretreatmentto ensure improved delivery accuracy. MR-Linacs are emerging as a potential solution to better visualize the softtissue pre-treatment as part of an image guided radiation therapy (IGRT) solution. MR is currently also used to define focaltumour regions within tumours such as the prostate. Little is known about the impact of these combined exposures underclinically relevant conditions, particularly in the presence of gadolinium-based contrast agents. Recent studies have shownthat gadolinium can act as a potential theranostic agent. If gadolinium could be used to enhance tumour visualizationduring IGRT and act as a radio-sensitizer at the same time, this could be a powerful tool to improve targeting and increasetumouricidal dose.This project will assess the biological impact of these combined exposures in a range of normal and tumour cell modelsquantifying DNA damage and cell survival endpoints. It will do this under clinically relevant exposure conditions, defined byNational Radiotherapy Standards and in the presence of the current clinical contrast agent to mimic current clinicalprotocols as well as future proofing the use of a nanoparticle formulation. It will access state-of-the-art combined MR-linacfacilities currently only available at NPL. This will allow a greater understanding of the potential benefits of combined-MRIradiation exposures and make prediction for future options for their clinical delivery.The project links the Advanced Radiotherapy Group at Queen's University Belfast with the commercial partner, theDosimetry Group at the National Physical Laboratory. It will make a significant contribution to NPLs work in this spaceaiming to define future National Standards for the use of combined MRI-radiation exposures and to maximise patientbenefit from these treatments. It will also validate the potential of gadolinium-based nanoparticles as radiosensitisers. Inthis project the student will benefit from a unique research experience by interacting with an industry leading company, theNational Physical Laboratory and actively contributing to the development of the MRI-Radiation Research Project. Theproposal is multidisciplinary across biology and physics giving the student insight and opportunity to gain unque expertisein the areas of preclinical radiotherapy research, dosimetry and radiation biology focussed on brain and prostate tumours.In addition, interaction with commercial partner will lead to interaction with other industrial and academic institutes whichmay include a research training visit to Christie Hospital Manchester and the Royal Marsden Hospital in London which willboth be commissioning clinical MRI-Linacs next year and Elekta, leading manufacturer in radiotherapy facilities who isdeveloping the first commercial MRI-Linac units.