Magnetic resonance spectroscopy in investigating the cancer metabolome in preclinical model systems

Glucose, lipid/phospholipid, and energy metabolism of cancer cells is profoundly altered compared with normal cells of the same tissue. Studies of cancer cell metabolism have led to the development of diagnostic techniques and molecular targeting of metabolic pathways to treat cancer, which can be monitored by these diagnostic techniques. Noninvasive imaging modalities such as magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT) can detect metabolic changes in cancers, with applications that span across the bench and bedside. MRS is the most versatile of these techniques because it also allows for high-resolution ex vivo approaches, which provide a detailed overview of several metabolic pathways in a single measurement in the tissue or cells under investigation. In addition, high-resolution ex vivo MRS can be combined with high-field in vivo MRS performed before excision of the tissue to provide in vivo metabolomic data sets of high spectral and spatial resolution (1). Some clinical areas in cancer management that can be integrated with in vivo MRS techniques are cancer diagnosis, identification of a suitable anticancer therapy, monitoring treatment delivery, and assessing response to treatment. Ex vivo MRS of tissue and cell extracts plays an important role in cancer drug discovery and basic cancer research, whereas high-resolution magic angle spinning (HR-MAS) MRS of biopsy specimens can be applied in clinical diagnosis. This chapter focuses on MRS methods that are available for investigating metabolic changes in cancer cells and animal models of cancer in vivo and ex vivo. Although the examples selected to illustrate the applications of magnetic resonance (MR) methods at the end of each section are from breast and prostate cancer studies, the methods can also be applied to study other types of cancer and can be adapted to investigate noncancerous cells and tissues.