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New imaging technique could predict whether primary breast cancer will spread to the lung (2017-08-18)

Scientists funded by the MRC, Breast Cancer Now and other collaborators have developed an innovative imaging technique that could predict whether breast cancer will spread to the lung.

In the study, published in Theranostics, researchers have demonstrated in mice that a new non-invasive imaging method can be used to detect changes in the lungs that signal breast cancer may soon spread there – before any metastases are visible.

If validated in humans, this approach could enable patients to be offered more intensive therapy earlier, to potentially prevent breast cancer spread.

Previous research has shown that the gathering of a special type of immune cell called ‘myeloid-derived suppressor cells’ (MDSCs) – in locations such as the lung – prepares the ground for breast cancer metastasis, by suppressing the local immune system and promoting the formation of new blood vessels (angiogenesis).

Researchers at King’s College London – in collaboration with teams at University College London and the University Hospital Muenster in Germany – have now developed a radioactive ‘tracer’ molecule to detect MDSCs accumulating in the lung in preparation for the arrival of breast cancer cells and the formation of metastases.

MDSCs are known to release a protein duo ‘message’ called S100A8/A9 which instructs the cells to gather in the lungs.
The gathering of these MDSCs in the lung causes inflammation, which makes it a favourable location for cancer cells to metastasise to.

The research teams – led by Dr Michel Eisenblätter and Dr Fabian Flores-Borja at King’s College London – hypothesised that, by making S100A8/A9 visible, it could be possible to identify when the lungs were being prepared for colonisation by breast cancer cells.

To test this theory, they developed a ‘tracer’ antibody able to attach itself to S100A8/A9, that can be detected using a special scan called SPECT (single photon emission computed tomography) – a 3D gamma-ray scanner.

The tracer releases radiation which can be distinguished by the SPECT scanner, highlighting areas where S100A8/A9 molecules, and MDSCs, are accumulating.

The researchers tested the tracer with triple negative breast cancer cells that had been implanted in mice, and were able to show – using a miniature SPECT scanner – that the ‘tracer’ lit up the lungs of mice well before any tumour cells were visible in the lung.

Furthermore, the tracer could distinguish between highly aggressive breast cancer with a high tendency to spread to the lung and tumours without metastatic potential.

Currently, to assess the risk of a patient’s breast cancer spreading, doctors use tools based upon the features of the primary tumour, such as tumour size and whether it has already invaded nearby lymph nodes.

With this early-stage study demonstrating the technique to be effective in mice, further studies are now required to develop a more effective ‘tracer’ molecule – better suited for use in humans – to be tested in clinical trials in future.

This work was also supported by the National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, KCL and UCL Comprehensive Cancer Imaging Centre, the German Research Foundation, Cancer Research UK, and the Engineering and Physical Sciences Research Council (EPSRC). The SPECT scanning equipment at KCL was funded by the Wellcome Trust.

For more information
Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment
Eisenblaetter M, Flores-Borja F, Lee JJ, Wefers C, Smith H, Hueting R, Cooper MS, Blower PJ, Patel D, Rodriguez-Justo M, Milewicz H, Vogl T, Roth J, Tutt A, Schaeffter T, Ng T.
Theranostics 2017; 7(9):2392-2401. doi:10.7150/thno.17138

Mrc Medical Research Council

King’s College London

University College London

Münster University Hospital (UKM)