More than half of cancer patients receive radiotherapy as part of their treatment, which is becoming increasingly personalised based on the predicted sensitivity of the tumour to radiation. In order to increase the accuracy of predictions, preclinical studies using small animals are needed to translate in vitro findings to the clinic. The predictive ability of animal models in preclinical radiotherapy studies is dependent on being able to deliver an accurate dose of radiation to the target tissue or organ. However, the actual dose of radiation delivered to the animal is not routinely measured and current dosimetry techniques measure the physical dose of radiation without consideration of the biological and physiological features of the animal. Tissue-equivalent and water phantoms can be used to measure absorbed dose, but have been found to produce inconsistent results compared to euthanised mice and rats. This is a major source of experimental error in preclinical studies.
Why we funded it
This PhD Studentship aims to develop a mouse imaging phantom using 3D printing technology suitable to accurately measure delivered radiation dose.
Guidelines from the Clinical and Translational Radiotherapy Research Working Group (CTRad) of the National Cancer Research Institute suggest a minimum of two cell lines from seven tumour types are needed for the evaluation of a single novel drug that induces radiation sensitivity. Seven to ten mice will be required per experimental group which results in an average of 120 mice needed for evaluation per drug. Accurate dosimetry of the delivered radiation dose to the animal will reduce experimental error and signal to noise ratio leading to a reduction in the number of animals required to generate statistical power. The potential for reduction will be calculated retrospectively by comparing studies using an accurate dose and those performed without dose measurement.
The imaging phantom to be developed in this proposal will mimic the size and structures of a mouse. Phantoms will also include purpose built cavities to house detectors or biological material, such as tumour tissue. These detectors use novel technology to detect radiation dose at a micrometre scale, which allows the determination of delivered radiation dose in tumour tissue compared to the normal tissue mimicked by the phantom. Radiation is affected by the density of tissue through which it passes impacting on the delivered dose of radiation. Phantoms currently are homogeneous and do not reflect this complexity. This project aims to also investigate the ability to 3D print phantoms of varying density to mimic the heterogeneous tissue densities within a mouse.
Principal investigatorProfessor Karen Kirkby
InstitutionUniversity of Manchester
Co-InvestigatorDr Amy Chadwick
Professor Kaye Williams
Dr Alexander Oh
Professor Chris Moore