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Modelling internal bone marrow dose from Radium-223


Project description

Metastatic castration resistant prostate cancer (mCRPCa) is an invariably fatal malignancy. It has a strong predisposition to forming bone metastases, with upwards of 90% of patients suffering these during their illness, often with bone being the only site of metastasis. A survival advantage was shown in the phase III trial ALSYMPCA where patients were treated with a bone-targeting a-emitting agent, namely radium-223 (223Ra). 223Ra is a calcium mimetic and it’s uptake into high-turnover areas of bone is not dependent on a particular malignant signalling process. It is therefore hypothesised that 223Ra could be of benefit in a range of malignancies with a predisposition to forming bony metastases such as breast, lung, kidney and myeloma and includes those with a favourable long-term survival probability. Accordingly there is a growing need for fundamental questions relating to the radiobiological risks of such internalised exposures to be addressed.

This study will use a range of endpoints to understand the biological action of 223Ra in vivo in humans and to address the question of long-term bone marrow (BM) complications, including therapy-related leukaemogenesis, of this treatment.

Impact statement

The use of radionuclides in targeted radiotherapy has great potential and could offer improvements in patient outcome and quality of life for a range of malignancies including those with a favourable long-term survival probability. However the potential risks of 223Ra remain uncertain principally due to the non-uniform dose distribution of a-particles in vivo and uncertainties in the bone marrow distribution of target cells for leukaemia induction. Outputs from this work will contribute to reducing these uncertainties and will inform on future dosing and treatment strategies.