Tumours generally display a preference for glycolysis over oxidative metabolism even in the presence of oxygen. This observation was first described by Warburg and has since been recognized as one of the hallmarks of cancer.1,2 The ATP supply derived from glycolysis has been suggested to be tightly coupled with the ATP demand required for Na/K ATPase activity,3,4 the membrane transporter responsible for pumping 3Na out and 2K into the cell for every molecule of ATP converted. There is evidence that Na/K ATPase could be a target for cancer therapy with breast cancer patients receiving cardiac glycosides such as digoxin showing distinct tumour cell morphologies, smaller tumour volumes at diagnosis, reduced metastasis after two years follow-up and reduced recurrence rate five years after mastectomy.5 The mechanisms underlying these observations are unclear, but there is evidence that Na/K ATPase, which is the principal inhibitory target for these glycosides, could be a therapeutic target for cancer treatment. The relationship between altered metabolism during tumorigenesis, Na/K ATPase activity and pathology is not well understood and there are currently no non-invasive clinically validated imaging tools of Na/K ATPase activity in cancer or in the heart. Despite significant advances in our understanding, the mechanisms underlying the Warburg effect remain poorly understood and imaging techniques still largely rely on 18FDG PET which reports on glucose transport and not downstream bioenergetics. In this PhD project we propose to develop a combination of in vivo imaging techniques employing 23Na MRI for imaging dysregulated sodium ion concentration in combination with 82Rb PET for probing Na/K ATPase activity in tumours and the heart to gain a better understanding of a fundamental aspect of tumour biology. In our laboratories we use in vivo preclinical disease models and isolated perfused rodent hearts to develop molecular imaging technologies to report non-invasively on biological processes using PET, SPECT, NMR spectroscopy and MR imaging. In this project, we will use these experimental models to test and develop 23Na MRI methods using a 9.4T Bruker MR system for in vivo imaging of sodium ion distribution and molecular imaging technologies employing a novel short lived PET radiotracer 82Rb to model the kinetics of membrane transport via the NaK ATPase in comparison with conventional radiotracers such as 18FDG PET as a surrogate of glucose metabolism. This project will train a biological or physical scientist in the skills that they need for a career in the imaging sciences and instill in them the mindset required to be able to design and carry out careful and robust validation and characterisation work. This project will expose the student to a large interdisciplinary team of academics, from whom they will acquire the surgical skills, animal husbandry and handling, biological assay development and histology skills, embedded in a department and a group where they will also learn about concepts in radiotracer design and evaluation, radionuclide imaging using PET and SPECT, data acquisition and pharmacokinetic modelling, Nuclear Magnetic Resonance, metabolomics and MRI. As such, we intend to educate and train a uniquely skilled, useful and versatile imaging scientist.