Invited Resubmission: Improved Organ Dose Determination and Imaging in 177Lu Targeted Radionuclide Therapy - towards a clinical solution.

Lead Research Organisation: University of Manchester
Department Name: Physics and Astronomy

Abstract

With this grant we will develop a far more accurate way of processing medical images from patients receiving cancer therapy using radioactive materials that target their tumours, known as Targeted Radionuclide Therapy (TRT). These images, taken using a hospital SPECT (Single Photon Emission Computed Tomography) scanner, are typically quite blurry and it is often difficult to distinguish tumours from normal healthy tissue. Based on our previous findings, by modelling the SPECT scanner system on a computer we will create a range of corrections that improve the accuracy of the information from these images.

Our collaboration has successfully shown that we can significantly improve this accuracy for a variety of simple models representing the human body. We now wish to use this work as the basis of an advanced technique which will provide the same improvements for data from more detailed models of the human body and ultimately for actual patients receiving cancer therapy. This information will be used to provide doctors with an accurate measurement of the radiation dose delivered to the tumours and critical organs in the patient's body.

Using current commercial SPECT images, the uncertainties in dose estimation do not allow treatments to be optimised and consequently a significant proportion of patients do not receive the optimal therapy. Identification of these patients is problematic due to the current low accuracy of dose measurements. Having this improved dose information will help doctors to improve their therapies, potentially reducing side effects and hospital stays. This will improve the patients' therapy experience and also improve the efficacy of the therapies by allowing the doctors to optimise the treatment for each patient. Only by improving the accuracy of the images obtained from the SPECT scanner can we provide this information.

Accurate dose information is considered very important in countries across Europe. Legislation is currently being written recommending accurate dosimetry for every patient receiving Targeted Radionuclide Therapy treatment. Our research will concentrate on improving the dose information for therapies using the isotope 177Lu. Recent work has shown that new treatments using this isotope can improve a patient's life expectancy by several years compared with other therapies, particularly for tumours affecting the hormonal and nervous systems.
Our research will provide the basis for developing a commercial solution that will allow the techniques developed from this grant to be used in clinical departments performing cancer therapy with 177Lu. However, it can be extended to cover the complete range of isotopes commonly used for therapy and for images from different models of SPECT scanner. We have already approached two commercial companies who are interested in helping bring this research to market. This has the potential to provide a significant improvement in the outcome of an estimated 201,000 such therapies performed annually in Europe.

Publications

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Price E (2019) Improving molecular radiotherapy dosimetry using anthropomorphic calibration. in Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)

 
Description We have discovered a way of optimising the correction methods used in image reconstruction for a clinical SPECT scanner. This was achieved by Monte-Carlo simulation of the scanner.
Exploitation Route We are working with an Industrial partner Hermes Medical Solutions Ltd who could ultimately market this research via a licence agreement once the full validation is achieved.
Sectors Healthcare,Other

 
Description We have employed detailed Monte-Carlo simulations to optimise the triple-energy windows used in 177Lu SPECT scatter correction. This has enabled a more accurate quantitative imaging which in turn provide better dosimetry for patients undergoing targeted molecular radiotherapy 177Lu therapy at The Christie. This should lead to improved patient prognosis as more optimised or patient specific healthcare may ultimately become possible with more accurate dosimetry.
Sector Healthcare
Impact Types Policy & public services

 
Description Change to clinical dosimetry procedure for low activity SPECT scans.
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Changed current practice for calibration Single Photon Emission Computed Tomography (SPECT) imaging.
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Clinical Implementation of Dosimetry in Molecular Radiotherapy - a European initiative.
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
Impact The work performed in ST/K002945/1 and ST/M004589/1 has provided a large part of the foundation of the EMPIR funded project "MRTDosimetry: Metrology for clinical implementation of dosimetry in molecular radiotherapy". This multi-national project if focused on the clinical implementation and it is strongly directed by the involvement of leading MRT clinics across Europe as well as building on metrology expertise. The project runs from 1st June 2016 to 31st May 2019 with a total budget of 2.2M euros and involves 18 partners, including 12 of the leading nuclear medicine centres in the EU, and 14 collaborating organisations including the University of Manchester. Expertise in 3D printing phantom production and SPECT calibration from STFC funded work allowed Dr Robinson to lead the development of the project work packages on Quantitative Imaging and Dosimetry comparison. To date this project has produced 6 peer reviewed open access scientific publications, 17 conferences presentations and posters and has engaged with 6 international standards bodies. An explicit example of work traceable to ST/K002945/1 and "Robinson et al, PMB, 61(14), 2016" are the protocols developed in the MRTDosimetry project for traceable quantitative imaging calibration for SPECT. This work has been incorporated into an upcoming IAEA Human Health Series Handbook on Dosimetry for Radiopharmaceutical Therapy. Further impact from ST/K002945/1 has been delivered by the delivery of a NHS HSST training lecture on "Optimisation of imaging with Monte Carlo simulation" which has formed part of this national training scheme since 2017. The research developed in this STFC funded work is now being developed as part of the UK National Measurement Service programme at NPL, supported by the worlds only dedicated nuclear medicine imaging metrology laboratory.
URL http://mrtdosimetry-empir.eu/wp-content/uploads/downloads/2017/05/MRTDosimetry-Publishable-Summary.p...
 
Description Influenced methods of personalised dosimetry for single photon emission computed tomography (spect).
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Invited Talk - (Robinson) Validation of calibration protocols and the MRTDosimetry project - EANM Annual Congress, Vienna, Austria
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Invited talk (Robinson) - MRTDosimetry: a new pan-european project for implementation of dosimetry in molecular radiotherapy. ICRM, LSWG, Buenos Aries, Argentina,
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Optimisation of 177Lu energy windows via Monte Carlo simulation
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact The triple energy window (TEW) scatter correction is widely used in clinical practise to improve image reconstruction and quantitative imaging (QI). Monte Carlo simulations can be used to deterimine the "true scatter", by tracking the path of gamma rays through the clinical geometry. By using this knowledge unrecoverable by experimental means, the triple energy window settings may be optimised to enable the best possible scatter correction for the 177Lu gamma emissions at 113 and 208 keV. This has already been implemented into clinical practise at the Christie and published to enable a wider scale adoption.
 
Description STFC Industrial CASE Studentship Panel (Dave Cullen)
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
URL https://stfc.ukri.org/funding/studentships/industrial-case-studentships/
 
Description STFC Industrial Case Award - Improving the image clarity and dosimetry accuracy for Selective Internal Radiotherapy using 90Y microspheres.
Amount £80,000 (GBP)
Funding ID ST/K005618/1 
Organisation Science and Technologies Facilities Council (STFC) 
Sector Public
Country United Kingdom
Start 09/2013 
End 09/2017
 
Description STFC Industrial Case Award - Validation of clinical radionuclide therapy dose distribution by a novel system of 3D printed anthropomorphic phantoms.
Amount £80,000 (GBP)
Funding ID ST/M003302/1 
Organisation Science and Technologies Facilities Council (STFC) 
Sector Public
Country United Kingdom
Start 09/2015 
End 10/2019
 
Title A custom made elliptical phantom (CATIE, the Christie Anatomical Tomographic Imaging Ellipse) 
Description A custom made elliptical phantom (CATIE, the Christie Anatomical Tomographic Imaging Ellipse) has been employed to scan a range of patient organ phantoms to investigate geometrical effects. 
Type Of Material Improvements to research infrastructure 
Year Produced 2013 
Provided To Others? Yes  
Impact The phantom was used at The Christie to allow new data to be collected. These data were analysed and resulted in 3 publications so far. 
 
Title Improvements to research infrastructure - High Throughput Condor Monte-Carlo Simulation Cluster 
Description To meet increasing demand for existing cluster resources, a further HTC cluster has been assembled. The additional cluster currently is comprised of 15 machine, totalling 284 threads at 2.4 - 4.0 GHz. Running CentOS 7 with access to the 4th floor ldap for hosted accounts, the cluster writes to a private NAS on a dedicated gigabit network. The primary purpose is simulation, with geant4.10.05 and OpenGATE 8.2 available. 
Type Of Material Improvements to research infrastructure 
Year Produced 2017 
Provided To Others? No  
Impact The work from patient anatomy MRT simulation has been published in Physica Medica (https://linkinghub.elsevier.com/retrieve/pii/S1120179719300134) and Nuclear Medicine Communications (Manuscript Number: NMC-11-2985R1, publication pending). 
URL https://personalpages.manchester.ac.uk/staff/ben.pietras/ithubschuster/mainSpace/home.html
 
Title New Gamma camera geometry simulation 
Description The GE Hawkeye Infinia 4 is a gamma camera currently in clinical operation for SPECT scanning at The Christie. This camera geometry has now been modelled inside of OpenGATE, to optimise for realistic back-scattering for higher energy photons. This model is now available to our group and used in multiple simulations. 
Type Of Material Improvements to research infrastructure 
Year Produced 2014 
Provided To Others? No  
Impact Using the exact geometry has enabled a more precise agreement of simulation to experimental data, validating MC as a tool to calculate dose for several radio-pharmaceuticals. 
 
Title A range of anthropomorphic phantoms, based on real patient CT data, has been manufactured through fused filament fabrication and scanned at The Christie 
Description A range of patient phantoms has been scanned using real patient distributions of 99*Tc and 177Lu to allow for validation of MC simulation over a realistic cohort. This experimental data may further be used to probe the efficacy of clinical image reconstruction software packages. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact The impact in validating MC simulation is the use of this to utilise patient specific s-factors, enabling an individual approach to MRT (molecular radiotherapy) dosimetry - with significantly greater accuracy than currently employed clinical models. 
 
Description Hermes Medical Solutions Limited 
Organisation Hermes Medical Solutions
Country Sweden 
Sector Private 
PI Contribution Non-DIsclosure agreement in place. We have shared informaiton on Monte-Carlo modelling and dosimerty.
Collaborator Contribution Hemes has shared information and have modified their commercial code to support our work. They have given us unique access to their code developers.
Impact Additional grant proposal currently in submission through the STFC CLASP Scheme
Start Year 2010
 
Description NPL 
Organisation National Physical Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution We have shared information on SOECT cameras calibration and nuclear physics knowledge.
Collaborator Contribution NPL has provided access to absolute calibration standards
Impact A new PhD student has been sponsored through this collaboration
Start Year 2016
 
Description The Christie NHS Foundation Trust, Nuclear Medicine Department. 
Organisation The Christie NHS Foundation Trust
Department Christie Medical Physics and Engineering
Country United Kingdom 
Sector Hospitals 
PI Contribution We have provided the physics expertise needed to deliver improved dose calculations for Molecular Radiotherapy treatments at The Christie. This work has combined existing expertise in Monte-Carlo simulation, from basic nuclear physics research, and novel new 3D printing techniques. This collaboration has already delivered improved activity quantification for MRT at The Christie which provide the foundation of accurate and optimised patient dose calculations.
Collaborator Contribution The Christie has provide access to anonymised patient data, clinical SPECT cameras, Molecular Radio Therapy (MRT) isotopes and current MRT dosimetry software which has allowed the techniques developed in this work to be translate to a clinical environment. The research output from this collaboration has provided improved activity quantification and validation of exiting MRT dosimetry software.
Impact This collaboration has delivered improved activity quantification for Molecular Radio Therapy at The Christie which provide the foundation of accurate and optimised patient dose calculations. The research output from this collaboration has provided improved activity quantification and validation of exiting Molecular Radio Therapy dosimetry software. The collaboration has submitted two research papers on this work.
Start Year 2009
 
Title Refinement of Hermes Medical Solutions Ltd. Dosimetry Software. 
Description .. 
Type Therapeutic Intervention - Radiotherapy
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2018
Development Status Under active development/distribution
Impact
 
Title Software for 3D printing and Geant simulation 
Description Software to convert between CT scan images and CAD drawing packages to that which can be printed by a 3D printer. 
Type Of Technology Software 
Year Produced 2016 
Impact We are being approached by other academics about producing 3D images and another group at The Christie hospital. 
 
Description Institute of Physics Annual Conference, Manchester 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Presented a talk on 90Y SPECT dosimetry.
Year(s) Of Engagement Activity 2015
 
Description Presented Poster at European Association Nuclear Medicine, Hamburg October 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presented poster which sparked conversations and discsussions about 90Y SPECT dosimetry
Year(s) Of Engagement Activity 2015
 
Description Presented Talk at internal Dosimerty Users Group meeting at The Christie Hospital NHS Trust, October 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Presented talk which sparked questions and debate about 90Y SPECT Dosimetry.
Year(s) Of Engagement Activity 2015
 
Description 'Speed networking' evening event for mums and year 8 daughters to give girls an idea of what a career in physics or engineering would be like. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact 'Speed networking' evening event for mums and year 8 daughters to give girls an idea of what a career in physics or engineering would be like. Around 40 mum-daughter pairs and 24 women in STEM attended (SP).
Year(s) Of Engagement Activity 2018
 
Description 'Speed networking' event for year 10 students from Whalley Range High School. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 'Speed networking' event for year 10 students from Whalley Range High School. Arranged through STEM ambassadors. Spoke to around 60 students for 4-5 minutes each about studying physics. Located at Connell Sixth Form College (SP - Sophia Pells).
Year(s) Of Engagement Activity 2018
 
Description 'Step into the future event' held at the University of Manchester for year 10 girls from Levenshulme High School. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 'Step into the future event' held at the University of Manchester for year 10 girls from Levenshulme High School. Spoke to small groups about studying physics and a PhD (SP).
Year(s) Of Engagement Activity 2018
 
Description 'Women In Physics Summer School'. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact 'Women In Physics Summer School'. Event for female physics undergraduates from the UK and Germany. Chatting to participants and discussing what a PhD is like and what my research is on (SP).
Year(s) Of Engagement Activity 2018
 
Description 3D printing for molecular radiotherapy dosimetry - IDUG/BIR conference on the future of molecular radiotherapy dosimetry, Oxford, UK, 2016 
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 The talk highlighted the use of 3D printing as a way to provide a more presonalised dosimetry for patients underoing SPECT. The talk was to the UK Internal User's Dosimetry Group and included clinicians and researchers working in SPECT dosimetry. The talk sparked several questions from the audience.
Year(s) Of Engagement Activity 2016
 
Description 3D printing for molecular radiotherapy dosimetry. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented talk at the IDUG/BIR conference on the future of molecular radiotherapy dosimetry, Oxford, UK, 2016 on the use of 3D printed phantoms in calibration and more accurate dosimetry with SPECT scanners.
Year(s) Of Engagement Activity 2016
 
Description Dalton Day symposium, The University of Manchester November 2014 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Presented talk to Dalton students who work in industry.
Year(s) Of Engagement Activity 2014
 
Description HeadStart Nuclear Physics Summer School. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact HeadStart Nuclear Physics Summer School. Gave a tour of the physics department to students and gave a talk regarding my research and my path into this PhD (SP).
Year(s) Of Engagement Activity 2018
 
Description Headstart lecture for lower-sixth students, at UoM 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Presentation and discussion of 3D printing applied to individual MRT dosimetry - BP.
Year(s) Of Engagement Activity 2017,2018
URL http://www.etrust.org.uk/headstart-inspire-ris
 
Description IPEM meeting on quant. SPECT imaging, Newcastle 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact IPEM meeting on quant. SPECT imaging - NC.
Year(s) Of Engagement Activity 2018
URL https://www.ipem.ac.uk/ConferencesEvents.aspx
 
Description MRTDosimetry workshop talk, Czech Technical University 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Third sector organisations
Results and Impact Discussion on MRT Dosimetry work undertaken at UoM and The Christie - NC.
Year(s) Of Engagement Activity 2018
URL http://mrtdosimetry-empir.eu/?page_id=210
 
Description MetroMRT (Molecular Radiotherapy) Workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented latest research developments to the EU EMPIR-MetroMRT project.
Year(s) Of Engagement Activity 2013,2014,2015
URL http://projects.npl.co.uk/metromrt
 
Description NPL MEMPHYS Workshop on Applications of 3D printing for medical phantoms 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk title: An individual approach to Molecular radiotherapy
dosimetry using 3D printed phantoms
Year(s) Of Engagement Activity 2017
 
Description Nuclear Head Start programme. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Presentation on applied nuclear medical physics research and associated career opportunities.
Year(s) Of Engagement Activity 2014,2015
URL http://www.etrust.org.uk/nuclear-physics-manchester
 
Description Nuclear Medicine Conference presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentations at:
1. British Nuclear Medecine Society annual meetings.
2. European Association of Nuclear medicine Congress.
3. International Conference on Medical Physics.
4. Nuclear Symposium on Science in Society.
Year(s) Of Engagement Activity 2013,2014,2015
 
Description Presentation to year 10 students describing my research area, Whalley Range High School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Presentation to year 10 students describing my research area (SP). Run by the Manchester INFUSE project (Lloyd Cawthorne)
Year(s) Of Engagement Activity 2018
 
Description Presented poster at British Nuclear Medicine Society, Brighton, April 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented poster which parked questions and debates afterwards.
Year(s) Of Engagement Activity 2015
 
Description Royal Sussex County Hospital, Gave talk on the work we've done at the Christie & UoM on Quantitative SPECT imaging 
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 Presentation on the work we've done at the Christie & UoM on Quantitative SPECT imaging - NC, Nick Calvert.
Year(s) Of Engagement Activity 2018
 
Description STEM Ambassadors event, Cheadle Hulme High School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact STEM Ambassadors event: SP gave three 20 minute presentations to three groups of students from years 7, 9, 10 and 12 about her PhD project as part of an after school program for students interested in science.
Year(s) Of Engagement Activity 2018
 
Description STEM Ambassadors event: 'Speed Networking' event with Key Stage 4 students, at Manchester Creative Studio. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact STEM Ambassadors event: 'Speed Networking' event with Key Stage 4 students. Short presentation about the group's research followed by general questions about PhD / studying physics.
Year(s) Of Engagement Activity 2017
 
Description Talk at IOP Nuclear Physics Conference, 3-6 April, University of Birmingham, Birmingham, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Presented talk at the IOP Nuclear Physics Conference, 3-6 April, University of Birmingham, Birmingham, UK.Talk entitles: Patient specific Monte Carlo dose calculations for 3D printed phantom studies
Year(s) Of Engagement Activity 2017
 
Description Talk at Radiotherapy Modelling Workshop at Luz Saint Sauveur 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented a talk at a workshop on radiotherapy modelling organised by the SFPM (Société Française de Physique Médicale). Dates: 21 - 24 September 2016. Talk title: 'Patient specific Monte Carlo dose calculations for 3D printed phantom studies in molecular radiotherapy'
Year(s) Of Engagement Activity 2016
URL http://luz2016.sfpm.fr/Luz/Welcome.html
 
Description Winner of online outreach activity- I'm a Scientist- Get me out of here! 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact An on-line activity where school students connect with scientists. A total of 3,863 school students from participating schools across the country could ask questions to scientists through live chats and the website. I was the winner in the "nuclear zone" which was supported by STFC. For winning I received £500 to put towards other outreach activities.
Year(s) Of Engagement Activity 2019
URL https://imascientist.org.uk/
 
Description Workshop: Headstart Summer school 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Talk title: An introduction to Nuclear medicine. Presentation to teachers at the "teach the teachers" meeting.
Year(s) Of Engagement Activity 2017