Cancer in the crosshairs: targeting cancer metabolism with hyperpolarized carbon‐13 MRI technology. (5th June 2018)

• Record Type: Journal Article
• Authors: von Morze, Cornelius; Merritt, Matthew E.
• Other Names: Jagannathan Naranamangalam R. guestEditor.
• Is Part Of: NMR in biomedicine. Volume 32:Number 10(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-06-05
• Subjects: dynamic nuclear polarization -- lactate -- metabolism -- pyruvate -- radiology -- Warburg effect; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3937
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Magnetic resonance (MR)‐based hyperpolarized (HP) 13 C 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 13 C 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 T 1, 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 13 C 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 13 C 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 13 C imaging will be highlighted, with an emphasis on both technological challenges and the biochemical aspects of HP experimental design. Abstract : Magnetic resonance based metabolic imaging has the unique advantage of chemical selectivity, but is handicapped by low sensitivity. Dynamic nuclear polarization amplifies MR signals by 104 or higher, allowing distinct reaction steps to be monitored in vivo with 13C MR methods. Cancer detection and grading is a primary goal of hyperpolarized imaging. This review highlights points of tumor metabolism controlling the appearance of hyperpolarized metabolite signals and discusses the hardware and pulse sequences necessary for imaging cancer on clinical systems. Glycolytic metabolism (orange), glutamine metabolism (pink), and access to fumarase (green), are current targets for hyperpolarized imaging.