Imaging and ‘omic’ methods for the molecular diagnosis of cancer

Abstract

Molecular imaging methods can noninvasively detect specific biological processes that are aberrant in cancer, including upregulated glycolytic metabolism, increased cellular proliferation and altered receptor expression. PET using the glucose analogue ¹⁸F-fluoro-2-deoxyglucose, which detects the increased glucose uptake that is a characteristic of tumor cells, has been widely used in the clinic to detect tumors and their responses to treatment; however, there are many new PET tracers being developed for a wide range of biological targets. Magnetic resonance spectroscopy (MRS), which can be used to detect cellular metabolites, can also provide prognostic information, particularly in brain, breast and prostate cancers. An emerging technique, which by hyperpolarizing ¹³C-labeled cell substrates dramatically enhances their sensitivity to detection, could further extend the use of MRS in molecular imaging in the clinic. Molecular diagnostics applied to serum samples or tumor samples obtained by biopsy, can measure changes at the individual cell level and the underlying changes in gene or protein expression. DNA microarrays enable high-throughput gene-expression profiling, while mass spectrometry can detect thousands of proteins that may be used in the future as biomarkers of cancer. Probing molecular changes will aid not only cancer diagnosis, but also provide tumor grading, based on gene-expression analysis and imaging measurements of cell proliferation and changes in metabolism; staging, based on imaging of metastatic spread and elevation of protein biomarkers; and the detection of therapeutic response, using serial molecular imaging measurements or monitoring of serum markers. The present article provides a summary of the molecular diagnostic methods that are currently being trialed in the clinic.

Keywords::

• gene expression
• magnetic resonance spectroscopy
• molecular imaging
• molecular profiling
• positron emission tomography
• protein markers
• serum markers

Financial & competing interests disclosure

Work in Kevin M Brindle’s laboratory is funded by a program grant from Cancer Research UK and the Leukemia and Lymphoma Society, USA. We are grateful to GE Healthcare for their funding and material support for our work with hyperpolarized ¹³C-labeled cell substrates. Kevin M Brindle has a consultancy agreement with GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.