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Title: Molecular imaging of tumours using dynamic nuclear polarization and magnetic resonance imaging
Author: Gallagher, F. A.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2009
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Dynamic Nuclear Polarization (DNP) is an emerging technique for increasing the sensitivity of Magnetic Resonance Imaging (MRI) in the liquid state. It has recently been applied to in vivo imaging of carbon metabolism: the spatial distribution of an injected hyperpolarized 13C-labelled molecule can be imaged in an intact living system, as well as the metabolites formed from it. This work demonstrates how this technique could have potential applications in medicine. 13C-labelled bicarbonate was hyperpolarized and the production of hyperpolarized carbon dioxide has been used to image tumour pH in vivo as well as the pH of the murine brain. An adaptation of this experiment allowed the spatial distribution of the enzyme carbonic anhydrase to be imaged in vitro and in vivo. Fumarate, a citric acid cycle intermediate, was hyperpolarized and its subsequent conversion into malate is shown here to increase with cellular necrosis in vitro; this was used as an early marker of response to chemotherapy both in vitro and in vivo. The metabolism of two other molecules is demonstrated: the in vitro metabolism of hyperpolarized 13C-labelled glutamine to glutamate as well as the metabolism of hyperpolarized 13C-labelled glutamate to α-ketoglutarate in vivo. Both of these present new ways to probe the citric acid cycle and the metabolism of glutamine may also act as a marker of cell proliferation. All of the molecules described here are endogenous and some are already administered intravenously into humans. There is therefore a realistic prospect that this technology can be translated into human imaging in the near future.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available