Repository logo
 

Imaging metabolism with hyperpolarized (13)C-labeled cell substrates.

Accepted version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Brindle, Kevin M 

Abstract

Non-invasive (13)C magnetic resonance spectroscopy measurements of the uptake and subsequent metabolism of (13)C-labeled substrates is a powerful method for studying metabolic fluxes in vivo. However, the technique has been hampered by a lack of sensitivity, which has limited both the spatial and temporal resolution. The introduction of dissolution dynamic nuclear polarization in 2003, which by radically enhancing the nuclear spin polarization of (13)C nuclei in solution can increase their sensitivity to detection by more than 10(4)-fold, revolutionized the study of metabolism using magnetic resonance, with temporal and spatial resolutions in the seconds and millimeter ranges, respectively. The principal limitation of the technique is the short half-life of the polarization, which at ∼20-30 s in vivo limits studies to relatively fast metabolic reactions. Nevertheless, pre-clinical studies with a variety of different substrates have demonstrated the potential of the method to provide new insights into tissue metabolism and have paved the way for the first clinical trial of the technique in prostate cancer. The technique now stands on the threshold of more general clinical translation. I consider here what the clinical applications might be, which are the substrates that most likely will be used, how will we analyze the resulting kinetic data, and how we might further increase the levels of polarization and extend polarization lifetime.

Description

Keywords

Carbon Isotopes, Humans, Male, Nuclear Magnetic Resonance, Biomolecular, Prostatic Neoplasms

Journal Title

J Am Chem Soc

Conference Name

Journal ISSN

0002-7863
1520-5126

Volume Title

137

Publisher

American Chemical Society (ACS)
Sponsorship
Wellcome Trust (095962/Z/11/Z)
The work in KMB’s laboratory on imaging metabolism with hyperpolarized 13C-labeled cell substrates is currently sup-ported by grants from Cancer Research UK (17242, 16465), a Wellcome Trust Strategic Award (095962) and a Marie Curie Initial Training Network (EUROPOL).