Improved radiopharmaceutical agents to detect and treat cancer in bones have been developed by UK scientists.

Philip Blower and colleagues from King's College London and Barts and The London School of Medicine made a dual function molecule containing a bisphosphonate to target bones and a radio-labelled part to image in just two steps. 

Cancer spreading from a tumour into bone, known as bone metastasis, is a common problem in cancer patients and can cause pain. Treatment involves injecting ^99mtechnetium or ^188/186rhenium bisphosphonates into the body. The bisphosphonates accumulate in the bone and treat the area and the radio-labelled metals aid imaging by single photon emission computed tomography. But technetium bisphosphonates exist as mixtures of compounds, making it difficult to establish each component's role, explains Blower. Rhenium complexes are easily degraded by enzymes, leading to lower bone uptake and higher radiation doses in soft tissue, he adds. 'Our motivation was to reduce these effects so that doctors are more likely to prescribe this form of treatment,' explains Blower. 'We would like ultimately to be able to give doses that are high enough not just to relieve pain but to treat the cancer and extend life expectancy.' 

In current treatments, the bisphosphonates both chelate the metal and bind to bone. Blower separated the bisphosphonate and metal with a spacer, which bound strongly to the metal leaving the bisphosphonate free to perform just one role - targeting bone. The two-step synthesis is easy and results in single, well-defined complexes.

'From a chemical perspective they're far superior to the agents we have already because we have a single compound and not a mixture of really unknown compounds,' says Blower of his molecules, 'and once we know what the chemistry is, it is under our control and we can optimise it and make it do what we want to do by changing the structure.' 

'It's interesting that a single-molecule complex with bisphosphonates accumulates in the bone matrix as it is commonly maintained that only polymeric species can do this job,' says Adriano Duatti, an expert in molecular imaging at the University of Ferrara, Italy. 'A truly remarkable achievement would be to produce the corresponding ¹⁸⁸Re complex in high specific activity, as currently, there is no effective ¹⁸⁸Re agent for the treatment of bone metastases.'

Ian Coates

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