Effects of Tumour Oxygenation on 13C Pyruvate Metabolism

Steven Reynolds¹, Samira Kazan², Joanne Bluff², Emily Wholey², Martyn Paley¹, Gillian Tozer²

The influence of tumour oxygenation state was determined by administering hyperpolarised 13C1-pyruvic acid (PA) and determining the conversion rate, kpl, to lactate. The tumours oxygenation state was concurrently monitored during MR experiments using invasive Oxylite fluorescent probes. P22 carcinosarcoma-bearing BD1X rats were anaesthetised and femoral cannulations performed for drug administration/blood pressure monitoring. Tumour pO2 was manipulated by supplying either normal air or hypoxia (10% O2, 4% CO2, balance N2). 5ml/kg of hyperpolarised 13C-PA was injected and slice-localised 13C spectroscopic data acquired using a 20mm 13C, 1H surface coil positioned over the tumour in a Bruker 7T MRI system Integral versus time responses curves for pyruvate and lactate were fitted to a one-way exchange model and kpl values extracted. Date for n=6 animals showed that rate of conversion of pyruvate to lactate, kpl, increases under hypoxic conditions.