For brain tumours, X-ray radiotherapy is used to reduce tumour bulk, treat inoperable tumours or secondary brain tumours. However, quality of life remains affected, and metastases and relapses still occur. Other, more targeted forms of radiotherapy are now being considered, including radionuclide therapy with Auger electron (AE)-emitters. This exploits the cytotoxicity of short-distance, low energy electrons emitted during radioactive decay; off-target effects are thus extremely unlikely. Also, simultaneous gamma emissions enable a theranostic approach by radionuclide imaging.
This project will carry out research into AE-emitting radionuclides, e.g. thallium-201, for glioblastomas. We showed that thallium-201 was the most lethal to cancer cells amongst AE-emitters; creating traditional tumour-targeting radiopharmaceuticals proved impossible though. We will explore how to target minimally invasive precision drug delivery systems placing multiple catheters into target areas in the brain to deliver AE-emitters directly through infusion. Any catheter placement requires patient/radionuclide-specific planning to maximise targeted delivery, ensuring treatment tumour coverage and minimising implantation-related risks.
1. Determine 2D and 3D spatial distribution requirements for AE-emitters for tumour control in glioblastoma cultures without affecting healthy cells
2. Create a mathematical model to predict treatment volume, i.e. radioactivity coverage
3. Determine from patient radiological scans where and how medical devices should be placed for local AE-emitter release
2D/3D cell culture, radiobiology, immunofluorescence microscopy, flow cytometry, SPECT/CT imaging, mathematical modelling, image processing
Year 1: healthy and cancer cell radioactivity uptake, specificity, and toxicity assays
Year 2: 3D spheroid work, toxicity, localisation methodologies, SPECT/CT imaging
Year 3: Create model to predict treatment volume using AE-emitter parameters including tissue diffusion parameters, toxicity, cell uptake and treatment parameters including catheter numbers and placement, infusion duration
Year 4: Incorporate model into planning using patient images for tumour geometry and patient-specific anatomy to ensure key regions, e.g. vessels, ventricles, are avoided during device placement