08 October 2013
A new modelling technique could allow doctors to track metabolic reactions in tumours in real time, allowing them to assess how well a treatment is working.
The new technique simplifies analysis of an innovative type of nuclear magnetic resonance (NMR) scan, which can measure the rates of metabolic chemical reactions in live cells, by removing the need for complex computer models of the reactions.
The research, by scientists at The Institute of Cancer Research, London, is published in the journal PLOS One, and could open up better ways of using drugs in patients.
NMR spectroscopy can be used to detect chemicals in tumours, but the signal intensity from standard NMR spectroscopy is too small to monitor reactions in real time, so researchers use a technique called dynamic nuclear polarization NMR (DNP-NMR).
DNP-NMR boosts the NMR signal by up to 10,000 times, allowing the rates of chemical reactions to be measured. However, this method is limited because it relies on computer modelling of the particular reaction being studied before use, making it a more complicated and time-consuming process.
To simplify the process and give the technique wider applications, scientists at The Institute of Cancer Research (ICR) have developed a new mathematical method for DNP-NMR - which compares the intensity ratios of the chemicals being studied, called the area under the curve (AUC) - forgoing the need for complex models.
Study co-author Dr Thomas Eykyn, a researcher in the Cancer Research UK and EPSRC Cancer Imaging Centre at The Institute of Cancer Research, said: “The ability to see chemical reactions taking place in live cells in real time is very exciting because it could help researchers developing cancer treatments assess their response.
“DNP-NMR is a promising technique, but previously it required a lot of complicated computer modelling which limited its uses. Our new method takes away the complications of using these models, simplifying DNP-NMR. We found that we could make the analysis much more straightforward which means this scan could be used more widely in the future, providing real benefits to doctors treating patients.”
The researchers tested their new DNP-NMR technique by injecting the metabolic compound pyruvate into cancer cells and watching as it was rapidly catalysed to form lactate by the enzyme lactate dehydrogenase.
They found that their new AUC ratio accurately measured the levels of pyruvate and lactate, showing a very strong correlation to the reaction rate calculated by the old modelling method. They found a similar correlation across several types of cancer cells and also in tumour models.
When they added an anti cancer drug which blocks an upstream signalling pathway that controls pyruvate to lactate exchange, they saw a drop in the AUC ratio equivalent to the decrease in the reaction rate calculated from the old model.