University of Cambridge > Talks.cam > Departmental Seminar Programme, Department of Veterinary Medicine > Detecting early tumour responses to therapy using magnetic resonance imaging and hyperpolarized spectroscopy

Detecting early tumour responses to therapy using magnetic resonance imaging and hyperpolarized spectroscopy

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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 death, since the level of tumour cell death immediately after drug treatment has been shown, in preclinical and clinical studies, to be a good prognostic indicator for treatment outcome. Thus 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.

The primary focus of our work has been the development of a targeted MRI contrast agent that binds to dying cells and recent progress with this agent will be described.

More recently, we have started to work with dynamic nuclear polarization (DNP) of 13C-labelled cell substrates, which offers gains in sensitivity of more than 104-fold, allowing sub second acquisition of 13C spectral data in vivo. Using DNP MRSI we have studied the metabolism of hyperpolarized [1-13C] pyruvate in an EL-4 lymphoma cells and in implanted EL-4 tumors, before and after treatment with the chemotherapeutic drug, etoposide. There was a significant reduction in lactate dehydrogenase-catalyzed exchange of 13C label between pyruvate and lactate in tumors 24 h after drug treatment. Images of intratumoral 13C pyruvate and 13C lactate showed a marked reduction in intensity in lactate/pyruvate ratiometric images. The decrease in exchange can be explained by a reduction in the lactate concentration in the tumor, a reduction in cellularity, and possibly decreases in intracellular coenzyme ( NAD ) and lactate dehydrogenase concentrations. The absence of any background 13C signal means that specific images of enzyme activity can be acquired. The lack of ionizing radiation, the use of an endogenous metabolite and a single imaging modality makes DNP 13C MRI an attractive potential tool for imaging the early responses of tumours to treatment in the clinic.

This talk is part of the Departmental Seminar Programme, Department of Veterinary Medicine series.

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