Detecting tumour responses to treatment with MRI
Kevin Brindle
University of Cambridge, UK
We have been developing non-invasive and clinically applicable magnetic resonance-based methods for detecting the early responses of tumours to therapy. A primary focus has been on the development of methods for detecting tumour cell apoptosis, or programmed cell death, since the level of tumour apoptosis after drug treatment has been shown, in preclinical and clinical studies, to be a good prognostic indicator for treatment outcome. Thus by monitoring tumour cell death an oncologist may get an indication of whether a particular drug is working very early during treatment, possibly within 24-48 hours, and long before there is any evidence of tumour shrinkage.
Sensitivity in the NMR experiment can be increased dramatically using nuclear spin hyperpolarization techniques (>10,000x). We showed recently that exchange of hyperpolarized 13C label between the carboxyl groups of lactate and pyruvate, in the reaction catalyzed by the enzyme lactate dehydrogenase, could be imaged in tumours and that this flux was decreased in treated tumors undergoing drug-induced cell death.
Since alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment. We have shown that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized H13CO3¯ and 13CO2 following intravenous injection of hyperpolarized H13CO3-. The technique was demonstrated with a study on a mouse tumour model, which showed that the average tumour pH was significantly lower than the surrounding tissue. Since bicarbonate is already used intravenously in humans, we propose that this technique could be used clinically to image tumours and other disease processes that are associated with alterations in tissue pH such as ischemia and inflammation.
Declaration of competing interest: Kevin Brindle has a research collaboration with GE Healthcare.
