Modelling internal bone marrow dose from Radium-223

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 uses 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.