Cancer in the crosshairs: targeting cancer metabolism with hyperpolarized carbon-13 MRI technology

Magnetic resonance (MR)-based hyperpolarized (HP) ¹³C metabolic imaging is under active pursuit as a new clinical diagnostic method for cancer detection, grading, and monitoring of therapeutic response. Following the tremendous success of metabolic imaging by positron emission tomography, which already plays major roles in clinical oncology, the added value of HP ¹³C MRI is emerging. Aberrant glycolysis and central carbon metabolism is a hallmark of many forms of cancer. The chemical transformations associated with these pathways produce metabolites ranging in general from three to six carbons, and are dependent on the redox state and energy charge of the tissue. The significant changes in chemistry associated with flux through these pathways imply that HP imaging can take advantage of the underlying chemical shift information encoded into an MR experiment to produce images of the injected substrate as well as its metabolites. However, imaging of HP metabolites poses unique constraints on pulse sequence design related to detection of X-nuclei, decay of the HP magnetization due to T₁, and the consumption of HP signal by the inspection pulses. Advancements in the field continue to depend critically on customization of MRI systems and pulse sequences for optimized detection of HP ¹³C signals, focused largely on extracting the maximum amount of information during the short lifetime of the HP magnetization. From a clinical perspective, the success of HP ¹³C MRI of cancer will largely depend upon the utility of HP pyruvate for the detection of lactate pools associated with the Warburg effect, though several other agents are also under investigation, with novel agents continually being formulated. In this review, the salient aspects of HP ¹³C imaging will be highlighted, with an emphasis on both technological challenges and the biochemical aspects of HP experimental design.