20th February 2018 - Imaging Tumour Metabolism in the Cancer Patient

Dear Colleagues,

We are pleased to invite you to attend a seminar presented by Professor Kevin M. Brindle from the University of Cambridge on Tuesday 20^th February 2018 2.00-3.00pm at 126 Mount Pleasant Room 209.

Imaging tumour metabolism in the cancer patient

Kevin M. Brindle, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK

 email: kmb1001@cam.ac.uk

Molecular imaging is likely to play an increasingly important role in predicting and detecting tumour responses to treatment 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 (reviewed in ¹).  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.  We also have used hyperpolarized [1-¹³C]pyruvate to investigate glycolytic metabolism in patient derived xenograft (PDX) models of glioblastoma.   These measurements have shown significant heterogeneity between tumours derived from different patients.   Metabolic imaging with hyperpolarized ¹³C-labelled cell substrates has recently translated to the clinic with a study in prostate cancer and we conducted our first clinical study in Cambridge using this technique in 2016.

1. Brindle, K.M. Imaging Metabolism with Hyperpolarized ¹³C-Labeled Cell Substrates. J. Amer. Chem. Soc. 137, 6418-6427 (2015).