Currently research activities fall into two main areas; the use of functional imaging techniques to quantify bone metabolism in patients with metastatic and metabolic bone disease and the investigation of the link between osteoporosis and cardiovascular disease. Over the last decade we have developed and refined the 18F-fluoride PET technique to enhance precision and reduce scan complexity and more recently have developed a unique method for quantitatively assessing bone metabolism at any site within the skeleton.
The research group combines extensive experience within the Division in the fields of metabolic bone disease, PET imaging, nuclear medicine, image processing and computational science to better understand the pathophysiology of metastatic and metabolic bone disease and the evaluation of novel drugs for the enhanced treatment of these patients.
Metabolic bone disease
The precision of 18F-fluoride PET is now comparable to that seen for conventional methods for measuring bone metabolism. We have completed a number of clinical studies examining the direct effects of antiresorptive and anabolic drugs on regional bone metabolism. We have demonstrated significant skeletal heterogeneity in bone perfusion and metabolism between skeletal sites. Differences have also been observed between patients with osteoporosis and healthy controls. We have also shown dissociation between PET parameters at the spine and global markers of bone metabolism. This research is timely as presently there is intense interest into the role of bone metabolism in the pathophysiology of osteoporosis.
We are one of only a handful of centres in the world involved in research utilizing radionuclide techniques for the evaluation of novel treatments for metabolic bone disease and certainly have the most expertise in this area. Recent work has included the use of 18F-fluoride PET and 99mTc-MDP plasma clearance methods to evaluate novel drugs developed for the treatment of osteoporosis and demonstrated how these techniques have the potential to be an important non-invasive biomarker for assessing treatment efficacy in early phase trials. Currently our research includes:
- The use of 18F-fluoride as a biomarker to assess early changes in bone metabolism at the hip in response to treatment for osteoporosis.
- An evaluation of the effects of bisphosphonate treatment withdrawal on regional bone metabolism using 18F-fluoride PET
- Validation of 18F-fluoride PET by direct comparison with the gold standard of bone biopsy.
Metastatic bone disease
Although conventional imaging methods exist for assessing response in bone metastases, it is recognised that these are relatively insensitive and it may be several months before a response can be measured, such that bone metastases are usually considered as non-measurable disease in clinical trials. There is therefore an urgent need for non-invasive methods to evaluate response at an earlier time to guide effective treatment in individual patients and to provide an early objective measure of response in skeletal metastases in a clinical trial setting.
Building on the research group’s experience of quantitative 18F-fluoride PET imaging in metabolic bone disease, we are planning to evaluate the role for this technique to act as an early response biomarker in patients receiving standard chemotherapy for prostate cancer. This builds on our pilot data that shows good correlations between 18F-fluoride PET parameters and serum tumour and bone markers. In refining the technique for imaging skeletal metastases, we anticipate that the method will be sufficiently robust to incorporate into future clinical trials of drugs targeting the skeleton.
In addition, a prospective comparison of 18FDG PET, 18F-fluoride PET and diffusion-weighted MRI is underway to assess early response of breast cancer bone metastases to endocrine therapy. It is anticipated that this study will also inform on the differing biological characteristics of osteoblastic and osteolytic disease and how the MRI parameters are affected by these processes.
In the future we plan to further characterise bone metastases by developing novel tracers as imaging biomarkers of osteoclast activity and evaluate their utility in measuring response to current and novel anti-osteoclastic therapies targeting bone metastases.
Osteoporosis and vascular calcification
The research group is also involved in the investigation of the association between bone density and vascular calcification and we are currently evaluating the potential of bisphosphonates, widely used to reduce fracture risk in patients with osteoporosis, to also simultaneously reduce arterial calcification.