Non-invasive molecular profiling of breast cancer with optoacoustic imaging
Supervisor(s): Dr Jeff Bamber, Professor Nandita deSouza and Dr Simon Robinson
Section: Joint Department of Physics
Team: Ultrasound and Optical Imaging
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Summary
In the management of cancer patients, there is a need to develop effective imaging of biomarkers for early detection, prognostic evaluation, prediction of therapy sensitivity or resistance and disease monitoring. In particular, cancer medicine is moving towards the concept of molecular profiling of the disease in individual patients, to plan and monitor treatment.
Markers for breast cancer aggressiveness (high proliferation rate, hypoxia, invasion, and/or metastasis) include the expression of cell-surface proteins such as HER2/neu (also known as ErbB-2), particularly when co-expressed with other factors (such as angiogenic growth factors, and loss of the tumour suppressor genes E-cadherin (CD324) [1], p53 or PTEN. HER2/neu is also important as a drug target (e.g. Herceptin, new HER dimerization inhibitors such as Pertuzumab and small molecule kinase inhibitors such as Lapatinib).
However, there are problems in that only some tumours possess these receptors (and the heterogeneity of expression within individual tumours is not documented), only some of them respond and nearly all tumours develop resistance. Non-invasive imaging of HER2/neu expression and distribution could provide much-needed early confirmation of the expression of the target in situ (and particularly in individual metastases) and whether the drug target has been hit. Repeated and frequent co-imaging of HER2/neu with other markers could provide important information on the development of resistance to treatment. Patients with primary breast cancer that tests negative for HER2/neu status, but where the metastases subsequently test positive, also could be more effectively assessed by such an imaging method.
Ultrasound is routinely used in the breast clinic, providing an excellent, low cost, rapid and safe method for imaging breast and other cancers but standard echography [2] lacks the ability to detect biomarkers such as those described above. The capabilities of ultrasound may be extended in this respect by the use of molecular imaging agents that provide selective contrast under optoacoustic detection. Optoacoustic imaging [3], which images optical absorption by detecting the pressure waves emitted when the tissue is illuminvivated with a short pulse of light, is able to detect the presence of intravenously administered contrast media such as gold nanoparticles that have been functionalised to bind to a cell surface molecular target of interest. The use of a nanoparticle of a specific size and shape bound to a specific antibody allows that particle to be distinguished from other particles (with different antibodies) using its spectral absorption signature [4]. This project will study in a preclinical context the feasibility of OA molecular profile imaging of breast cancer, and obtain an indication of its likely areas of usefulness. It is part of a collaborative effort within the ICR’s Imaging Centre funded by the CRUK, and will extend an international collaboration between five European partners that was started with EU Framework 6 funding [5]. This established a working real-time OA imaging system, sources for gold nanoparticles, methods for functionalising them and showed that they could be visualised in vivo.
References
- Wirapati, P., et al. (2008) Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res. Vol 10, No 4: R65. doi: 10.1186/bcr2124
- Sehgal, C, et al. (2006) A Review of Breast Ultrasound. J Mammary Gland Biology & Neoplasia Vol 11, No 2, p113-123
- Wang, L. (ed.) (2009) Photoacoustic Imaging and Spectroscopy. ISBN 1420059912. CRC Press, Boca Raton
- Li, P-C, et al. (2008) In vivo photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods. Optics Express Vol 16, No 23, p18605-18615
- ADONIS website (2009) Accurate Diagnosis of prostate cancer using Optoacoustic detection of biologically functionalized gold Nanoparticles - A new Integrated Biosensor System
