Metabolic Tumor Imaging Using Magnetic Resonance Spectroscopy

Abstract

The adaptability and the genomic plasticity of cancer cells, and the interaction between the tumor microenvironment and co-opted stromal cells, coupled with the ability of cancer cells to colonize distant organs, contribute to the frequent intractability of cancer. It is becoming increasingly evident that personalized molecular targeting is necessary for the successful treatment of this multifaceted and complex disease. Noninvasive imaging modalities such as magnetic resonance (MR), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) are filling several important niches in this era of targeted molecular medicine, in applications that span from bench to bedside. In this review we focus on noninvasive magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) and their roles in future personalized medicine in cancer. Diagnosis, the identification of the most effective treatment, monitoring treatment delivery, and response to treatment are some of the broad areas into which MRS techniques can be integrated to improve treatment outcomes. The development of novel probes for molecular imaging—in combination with a slew of functional imaging capabilities—makes MRS techniques, especially in combination with other imaging modalities, valuable in cancer drug discovery and basic cancer research.

Proton MR spectroscopic imaging of human glioblastomas at 1.5 Tesla

“…These changes are further accompanied by increased inhibition of mitochondrial metabolism, i.e. reactions in Krebs cycle as well as in respiratory chain (Diaz-Ruiz et al 2009;Frezza and Gottlieb 2009), and ultimately, by greather production of lactate (Cairns et al 2011;Glunde and Bhujwalla 2011). A significant increase of Lac/ tCr ratio was found also in this study.…”

“…Since the tNAA is synthesized in neuronal mitochondria it is regarded as a marker of neuronal viability and function (Soares and Law 2009;Barker 2010). However, tNAA is not a sufficiently specific marker for glioblastomas (Laprie et al 2008;Horska and Barker 2010), its decline reliably indicates the loss of healthy neurons in the tumor-affected brain tissue (Glunde and Bhujwalla 2011;Kao et al 2013). To the tCho signal mainly phosphocholine contributes, and in a lesser extent glycerophosphocholine, free choline, and acetylcholine (Horska and Barker 2010;McKnight and Wladman 2010).…”

“…triacylglycerols and cholesterol esters accumulated in lipid droplets (Opstad et al 2008;Walther and Forese 2009). The exact role of lipid droplets in the brain is not fully understood, but they are believed to be reservoirs of fatty acids arising as a waste product during degradation of cellular membranes in the necrotic tissue (Toyooka et al 2008;Walther and Forese 2009;Delikatny et al 2011) as well as in tumor cells, in which the apoptosis has been initiated (Opstad et al 2008;Glunde and Bhujwalla 2011). Although the evidence of spectroscopically detectable differences of metabolite concentrations in the tumors compared to the normal brain tissue (McKnight and Wladman 2010;Kumar et al 2012;Pinker et al 2012) was demonstrated, the clinical application of 1 H MRS for examination of intracranial tumors has until recently been somewhat limited.…”

Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

“…Aberrant phospholipid metabolism of cancers (5), associated with upregulation of ChKa, a biomarker of malignant transformation (1), has been studied using proton and phosphorous MR spectroscopy (MRS) of tumor tissue biopsies and noninvasive tissue measurements (20). The inherently poor sensitivity of MRS in vivo precludes resolution of individual choline metabolite resonances.…”

Tumor cell plasticity: the challenge to catch a moving target

“…Cell plasticity is hard to track, due to its transient character and high reversibility depending on the surrounding conditions, and cannot be captured in a representative way by the snapshot of a classic tumor biopsy and subsequent histological analysis. One approach to evaluate cell state dynamics and plasticity may be in vivo non-invasive molecular imaging, as hypoxia, apoptosis, acidosis, cell signaling and inflammation can be considered, which are all important factors accounting for a high plasticity [104,105].…”