Developing a technique to measure levels of tumour hypoxia during proton beam therapy through gamma-ray spectroscopy

Lead Research Organisation: University of Manchester


Around 50% of patients receive radiotherapy as part of their cancer treatment. One of the most important factors influencing clinical outcome, following radiotherapy, is tumour hypoxia. Low oxygen levels (hypoxia), is a characteristic of the tumour microenvironment which drives increased metastatic potential and confers resistance to radiotherapy, decreasing overall survival. However, even with advances in radiotherapy, including a move towards proton beam therapy (PBT), hypoxia-mediated radio-resistance is a complexity that remains. This project aims to develop a technique to measure oxygen levels, and consequently hypoxia, in tumours treated with PBT in real time. During PBT, dose is deposited in tissue by both the ionisation of atomic electrons and proton interactions with the atomic nuclei. This project takes a multidisciplinary approach to harness the naturally produced radiation during PBT to measure hypoxia. Real time measurement of hypoxia during treatment will inform adaptive therapy where radiation dose can be escalated to overcome hypoxic radio-resistance during fractionated treatment planning.

Planned Impact

A real-time, non-invasive measurement of whole tumour hypoxia has a clear clinical benefit and a simple clinical detection device could be developed. Follow-on funding would be used to further the technique to not only ascertain tumour hypoxia levels as a whole but to map the regions of differing hypoxia within a tumour. This will be achieved through a multi-detector system that can determine the gamma-ray origins using energy and time-of-flight information. This multi-detector clinical device will enable hypoxia mapping in 3 dimensions and guide dose escalation in those radiation resistant hypoxic regions in the tumour. This advancement would drive adaptive therapy whereby the treatment plan could be modified during the fractionated course of treatment to optimise the dose distribution being delivered. The proton therapy research group (of which the PI and CI's are members) currently collaborate with members of the treatment planning team at the Christie Hospital on plan optimisation and adaptive therapy.


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Title Monte-Carlo simulation of oxygen spectra from low oxygen media 
Description The model has been created using the Geant4 Monte-Carlo radiation transport simulation framework. The model produces a spectrum of oxygen gamma rays produced when a proton beam impinges a flask of fluid held under differing oxygen tensions. 
Type Of Material Computer model/algorithm 
Year Produced 2022 
Provided To Others? No  
Impact This model is helping to assess the sensitivity of the proposed technique and is helping to inform and improve the upcoming experimental work 
Description University of Birmingham 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Performed some measurements at the cyclotron laboratory at the University of Birmingham. Rented a hypoxia cabinet which resided there too for collaboration use. Developed a CRUK Mulit-disciplinary grant proposal with these collaborators.
Collaborator Contribution Allowed use of the cyclotron to deliver a proton beam to our samples. Allowed use of some of their LaBr detectors and electronics during the measurements.
Impact A follow-on proposal for CRUK funding was developed. This was, however, unsuccessful. This collaboration is mulit-disciplinary with the following disciplines involved: Nuclear Physics, Medical Physics, Proton Therapy Physics, Radiobiology
Start Year 2018
Title LaBr scintillator detectors 
Description 16 LaBr scintillator detectors have been acquired to improve the detection of oxygen gamma rays during proton irradiation. 
Type Of Technology Detection Devices 
Year Produced 2022 
Impact The impacts are yet to be seen but it is envisaged that the sensitivity of the proposed technique will be greatly enhanced by this increase in the number of radiation detectors 
Description STEM Quantum Ambassador school talks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Gave a presentation on proton therapy research, as part of the STEM Quantum Ambassador programme, which included work around the grant topic to secondary school Y12 and 13 students. This was requested by the schools due to the surge in interest in medical physics amongst A level students. A question and answer session followed the presentation.
Year(s) Of Engagement Activity 2022