Development of a biologically-relevant preclinical radiotherapy dosimetry phantom

This project aims to develop a zoomorphic phantom which mimics the size, physiological features and tissue densities of a mouse, which can be routinely used as a surrogate to measure the delivered radiation dose, addressing the unmet need identified in pre-clinical radiation research, from the animal perspective. Furthermore, the novel phantom will carry biological material that is relevant to the tissue being irradiated to assess biological dose and feature novel detector technology aiming to have sufficient spatial resolution to compare physical dose and biological effect at the micron scale. Ultimately, this tool could be used as a national standard to aid standardisation in preclinical dosimetry QA between centres, with the 3Rs potential to reduce error, chance of toxicity and ultimately reduce animal numbers required, whilst scientifically building confidence and reproducibility in results.

This project will further develop the concept of the zoomorphic 3D printed phantoms generated in the preliminary studies. A multidisciplinary approach will be taken between medical physics, particle physics and translational radiobiology to develop distinct aspects of the phantom that together, will provide a novel tool incorporating accurate detection of radiation dose, tissue specific densities and biological relevance by addressing the following objectives:

1. Development of 3D diamond detector technology (for example 3D diamond but could also include liquid scintillator detectors) (Lead: Dr Alex Oh, Manchester Particle Physics Group)
Development and validation of detector technology capable of detecting radiation dose at micrometer scale resolution. Allow determination of delivered radiation dose with spatial resolution to detect dose in tumour vs normal tissue, and determine the impact of physical dose on biological effect.

2. Biological relevance (Lead: Dr Amy Chadwick, Institute of Cancer Sciences)
Design to include specific pockets suitable to carry biological material, for instance tumour or normal tissue cell lines in 3D matrices. Biological end points will include those deemed gold standards in radiation research and those which have been shown to correlate with physical radiation dose, as listed in guidelines from the European Network in Biological Dosimetry (10).

3. Mimicking tissue-specific densities (Lead: Professor Gareth Price with Giuseppe Schettino (NPL) Andrew Robinson (NPL), The Christie Medical Physics and Engineering)
The path of radiation through tissue is affected by the density of tissue that the radiation passes through, therefore affecting the delivered dose of radiation. The project, carried out with colleagues at NPL will aim to investigate the ability to 3D print phantoms of varying density, to mimic the heterogenous tissue densities in a mouse. It will also investigate developing tissue equivalent materials for proton therapy.

4. Validation (Lead: Professor Kaye Williams, Manchester Pharmacy School, Adam Aitkenhead The Christie)
The novel phantoms will be tested using the Small Animal Radiation Research Platform (SARRP, Xstrahl). Particular attention will be given to imaging setup and treatment planning. Validation could include comparison of dose measurement between different radiation types, including proton beam therapy, available in Manchester in 2018. Through 5M Euro H2020 integrating action INSPIR (currently under negotiation) there is an opportunity to conduct inter-comparison studies with other proton therapy centres in Europe