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Imaging cancer metabolism - Out of the lab and into the clinic

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Imaging the metabolism of tumours is likely to play an increasingly important role in predicting and detecting tumour responses to treatment and thus in guiding treatment in individual patients. Magnetic resonance spectroscopy and spectroscopic imaging has long been used to study non-invasively the metabolism of tissues in the human body. The problem is that it is a very insensitive technique which means that the resolution of the images is poor and examination times can be very long. We have been using a technique, called dynamic nuclear hyperpolarization (DNP), which can increase sensitivity in the MRI experiment by >10,000x. In this technique we “hyperpolarize” 13C-labelled substrates, such as glucose, and then inject them intravenously. 13C is a non-radioactive isotope of carbon that can be detected in the MRI experiment. The massive increase in sensitivity afforded by hyperpolarization of the 13C nucleus means that we can image the location of the labelled substrate in the body and its metabolic conversion into downstream metabolites. A former colleague once said that it allowed us to watch tumours “eat and breath” and most importantly we can also watch them die when a therapy is effective. In this lecture I will describe the work that we have done using this technique over the last 15 years, which has taken it from the lab and into the clinic. I will finish by describing a new MRI technique for imaging tumour metabolism, which has also recently gone into the clinic and that uses deuterium (2H)-labelled substrates (2H is a non-radioactive isotope of hydrogen that can also be detected in the MRI experiment). 2H is even less sensitive to MRI detection than 13C and is not suitable for hyperpolarization. In this case we exploit an NMR property of the 2H nucleus which allows us to acquire signal very rapidly without signal saturation, which compensates for the low sensitivity of detection. I will show how we think that this can provide complementary information to that provided by imaging with hyperpolarized 13C-labelled substrates.

This talk is part of the Cambridge Philosophical Society series.

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