Abstract

Imaging Tumour Metabolism with Hyperpolarized 13C-labelled Cell Substrates

Kevin Brindle, Professor, University of Cambridge

A better understanding of tumour biology has led to the development of targeted therapies, in which a drug is designed to disrupt a specific biochemical pathway important for tumour cell survival or proliferation. The introduction of these drugs into the clinic has shown that patients can vary widely in their responses. Molecular imaging is likely to play an increasingly important role in predicting and detecting these responses and thus in guiding treatment in individual patients. We have been developing methods for detecting the early responses of tumours to therapy, including metabolic imaging with hyperpolarized 13C-labelled substrates, which we have used both to detect treatment response and to investigate the tumour microenvironment. Exchange of hyperpolarized 13C label between lactate and pyruvate and net flux of label between glucose and lactate have been shown to decrease post-treatment and hyperpolarized [1,4-13C]fumarate has been shown to detect subsequent cell necrosis. Tumour pH can be imaged using hyperpolarized H13CO3¯ and redox state can be determined by monitoring the oxidation and reduction of [1-13C]ascorbate and [1-13C]dehydroascorbate respectively. More recently we have shown that we can follow, using hyperpolarized [1-13C]pyruvate, the progression of pancreatic precursor lesions, in a genetically engineered mouse model of the disease, which potentially could be used clinically to guide earlier intervention. Metabolic imaging with hyperpolarized 13C-labelled cell substrates has recently translated to the clinic with a study in prostate cancer and we expect to conduct our first clinical studies in Cambridge using this technique later this year.