Development of a multipurpose small animal phantom for pre-clinical radiotherapy studies

Lead Research Organisation: University of Hull
Department Name: Biomedical Sciences


The initial aim of the project is to establish a commercial dosimetry service for pre-clinical radiobiology studies which will i)
improve the data and accuracy of experiments via provision of state of the art dosimetry, ii) reduce the total number of
animals used and iii) provide a novel 3D tissue-based platform for study of radiosensitizers.
This will be achieved through the development of standardized dosimetry protocols that will reduce dose uncertainties, and
the development of a multipurpose small animal phantom. A number of different irradiation units are currently employed
across the UK using their own dosimetry schedules, therefore as part of establishing the new service a comprehensive
audit of current practices will be undertaken. Due to the steep dose responses in radiation studies a 5% reduction in dose
uncertainty would roughly halve the number of animals required to achieve the same statistical relevance. The definition of
standards and quality assurance procedures for radiobiological studies will help regulate preclinical radiotherapy activities.
This will increase the confidence of clinical researchers and the funding bodies in such methods, as well as opening new
market opportunities for dosimetry services offered by the National Physics Laboratory (NPL). The proposed new
dosimetry service for pre-clinical imaging will scale-down established methodologies from the clinical to provide confidence
and accuracy for pre-clinical work, bringing the latter up to the same standard as the existing provision for patients. As a
major supplier of x-ray equipment, Xstrahl Ltd will benefit from an increase in radiobiological studies as the economic and
methodological barriers to entry are lowered.
A unique type of phantom will also be developed that is capable of housing a bespoke microfluidic device, containing a
tissue biopsy that will offer an alternative in vivo-like option for radiation-drug synergistic studies. The phantom will contain
tissues slices, e.g. 4mm x 4mm x 0.2mm from xenograft models or human biopsies and these can then be used to
measure the effects of irradiation with or without drugs, under precisely controlled conditions. Furthermore these tissue studies will incorporate all the improved dosimetry measurements thus significantly improving the experimental accuracy.
The project addresses issues identified by research organisations, funding bodies and the clinical community and opens up
new business opportunities for NPL, improvements in technology for Xstrahl Ltd and licensing or spin-out options for the
University of Hull.

Planned Impact

The National Physics Laboratory (NPL) aims to develop and implement a traceable dosimetry service for pre-clinical
radiobiological studies for both the commercial and research markets. The service will include dosimetry traceability to
national standards, full source characterization, specific Quality Assurance procedures and in vivo dose verification based
on an innovative phantom with the option of encompassing a microfluidic device. The principle impact of the project will be
with the large radiobiological and pre-clinical research centres. There are ~10 main radiobiological centres in the UK and
over 50 research units performing radiation related research. Eight of the 15 CR-UK supported centres have radiationbased
research as a key aspect of their treatment strategies. In addition, many Commercial Research Organisations
(CRO) such as Epistem as well as the main radiobiological centres, have bases in Germany, Sweden, Netherlands, Italy,
and France. Over 140 centres were represented at the last European Radiation Research Society and the H2020 portfolio
for radiobiological work in EU is >Euro15M/year. Provision of a dosimetry service to satisfy regulatory compliance and
improve the research value will generate higher quality data, at a lower cost and using less animal experimentation.
Opening up NPL's dosimetry services to a new market will increase sales to NPL;. with a projected increase in sales of up
to £250k/year in the first years of the new service. Since there is no such service or platform currently available on the
world-wide market, this represents an excellent opportunity for NPL in terms of offering new services and increasing the
highly-skilled UK work-force.

The work will also have a major impact on the manufacturers of radiation facilities; who will benefit from the dosimetry
service for adherence to specification compliance. The X-ray irradiator for scientific and industrial research laboratory
market is dominated by Xstrahl (the project partner), Faxitron, Precision X-ray and Rad Source each currently supplying
~1000s cabinet systems worldwide. Moreover, they provide a range of collimators, filters, animal retainers and chambers
which will affect the dose absorbed by the animal/sample therefore requiring specific measurement and dose validation.
These companies will benefit from the increased awareness of the importance of radiation dosimetry and adjunct credibility
in radiation products and core services for both new and existing pre-clinical sites. The new tissue based phantoms will
provide a platform that allows biomedical researchers to undertake radiobiology research without the need for substantial
investment in large animal facilities and irradiation equipment. The validated dosimetry and accurate monitoring mean that
fewer animal experiments will be required to obtain the same level of data, and most importantly the technology
encourages the replacement of animals where human tissue is available, helping the UK stay at the forefront of research
whilst fully adopting the NC3Rs ethos.
Regulatory bodies have previously highlighted the need for standardization of pre-clinical work, the outcomes of the
proposed work will provide both a knowledge framework and also the monitoring service that can deliver the technology.
As part of the project there will be early engagement with the appropriate authorities to ensure that all the relevant data are
gathered and that the findings can quickly transform and improve the radiobiology field. It is envisaged that changes can
be made within two years of the project's completion.
Description A small animal phantom has been characterised and produced that can be used, in place of animals, when both calibrating or training new users on pre-clinical irradiators. The units can be purchased and the dosimetry service will be provided through NPL.
Exploitation Route Additional work is being undertaken to arrange the service between NPL and Xstrahl.
The mouse phantoms are available for sale from Leeds Test Objects and 1 has been sold to a University installing an Xstrahl machine in the USA.
Sectors Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Other

Description The phantom produced and characterised through the grant activity can now be purchased through Leeds Test Objects - a company that has formed a formal partnership with the research groups. NPL are in discussions with Xstrahl about offering a service to calibrate small animal irradiators. They are offering the measurements as a "consultancy" for the next 6-9 months to asses the level of interest; and will review the case in July 2020; no advance due to Covid. Two of the mouse phantoms have been sold by the commercial partner since Feb 2021. An additional 2 mouse phantoms have been sold by the commercial partner since Feb 2022
First Year Of Impact 2021
Sector Pharmaceuticals and Medical Biotechnology,Other
Impact Types Economic

Description The project was presented to a government delegation to NPL led by Sir Mark Walport
Geographic Reach National 
Policy Influence Type Contribution to a national consultation/review
Title The Leeds Micro CT Mouse Phantom 
Description The Leeds Micro CT Mouse Phantom is a tissue mimicking, pontikiomorphic (in the form of a mouse) phantom for use in demonstrating and assessing image quality of pre-clinical MicroCT scanners. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact Two of these phantoms have been sold as a commercial product. 
Description Dr Ileana Silvestre gave a talk about end-to-end dosimetry test, developed during the Innovate UK project at the 5th Conference on Small Animal Precision Image-guided Radiotherapy (Munich) March 9-11, 2020 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This international conference shared information about the need for accurate dosimetry in small animal irradiators.
Year(s) Of Engagement Activity 2020
Description Ileana Silvestre and Anna Subiel have presented outputs of the InnovateUK project at the 16th International Congress of Radiation Research (Manchester) 25-29th of August. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Additional academic centres have been in contact and wish to use the device and service.
Year(s) Of Engagement Activity 2020
Description NPL organized a 2-day workshop on 3D printing for clinical and pre-clinical applications at NPL 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A number of attendees have asked to be kept updated on the progress of the work as they are keen to adopt the technology.
Year(s) Of Engagement Activity 2017