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

Magnetic resonance imaging (MRI) is used throughout radiotherapy due to excellent soft tissue contrast aiding delineation
of the tumour in a variety of treatment sites. MRI is generally considered a safe technology with very high clinical impact. It
is accepted as a powerful non-invasive diagnostic tool to investigate the anatomical structures and functions in the body, in
both health and disease. It is estimated that 200 million MRI scans have been performed worldwide and no direct adverse
biological effects have been reported in subjects/patients. Radiotherapy is a highly effective treatment for a wide number of
disease sites and plays a major role in 50% of all cancer treatments. Recent technological advances have allowed
treatments which conform better to the tumour while avoiding normal tissue. This improved conformity often requires
improved image guided radiotherapy (IGRT) generally performed using cone beam CT (CBCT) scans taken directly pretreatment
to ensure improved delivery accuracy. MR-Linacs are emerging as a potential solution to better visualize the soft
tissue pre-treatment as part of an image guided radiation therapy (IGRT) solution. MR is currently also used to define focal
tumour regions within tumours such as the prostate. Little is known about the impact of these combined exposures under
clinically relevant conditions, particularly in the presence of gadolinium-based contrast agents. Recent studies have shown
that gadolinium can act as a potential theranostic agent. If gadolinium could be used to enhance tumour visualization
during IGRT and act as a radio-sensitizer at the same time, this could be a powerful tool to improve targeting and increase
tumouricidal dose.

This project will assess the biological impact of these combined exposures in a range of normal and tumour cell models
quantifying DNA damage and cell survival endpoints. It will do this under clinically relevant exposure conditions, defined by
National Radiotherapy Standards and in the presence of the current clinical contrast agent to mimic current clinical
protocols as well as future proofing the use of a nanoparticle formulation. It will access state-of-the-art combined MR-linac
facilities currently only available at NPL. This will allow a greater understanding of the potential benefits of combined-MRI
radiation 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, the
Dosimetry Group at the National Physical Laboratory. It will make a significant contribution to NPLs work in this space
aiming to define future National Standards for the use of combined MRI-radiation exposures and to maximise patient
benefit from these treatments. It will also validate the potential of gadolinium-based nanoparticles as radiosensitisers. In
this project the student will benefit from a unique research experience by interacting with an industry leading company, the
National Physical Laboratory and actively contributing to the development of the MRI-Radiation Research Project. The
proposal is multidisciplinary across biology and physics giving the student insight and opportunity to gain unque expertise
in 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 which
may include a research training visit to Christie Hospital Manchester and the Royal Marsden Hospital in London which will
both be commissioning clinical MRI-Linacs next year and Elekta, leading manufacturer in radiotherapy facilities who is
developing the first commercial MRI-Linac units.