A new generation of radioactive tracers will let doctors watch how cancer cells burn fat and store energy inside the living human body, without cutting a single piece of tissue. Current methods for studying tumour metabolism rely on biopsies, which disturb the tissue and can miss important variations within a tumour. PET scans can see molecular activity non-invasively, but the field is held back by a shortage of validated probes that work safely in people. This programme will introduce two new imaging probes into humans and complete work on a third. These probes detect fatty acid oxidation, glycogen storage, and the synthesis of membrane precursors—three metabolic pathways that tumours reprogramme to fuel their growth. If successful, the research will give scientists a direct window into how cancer rewires its metabolism in its natural environment. This could improve the design of drugs that target metabolic vulnerabilities, and the probes themselves may eventually help clinicians monitor whether a patient’s tumour is responding to treatment. The work is translational: it connects chemistry design, automated synthesis, regulatory approval, mathematical modelling, and pathology validation into a single pipeline. The immediate outcome is a set of tools for fundamental investigation of human disease biology, with the potential to feed into patient management.
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Our group is interested in discovery and development of novel radiotracers for probing disease biology. In this quinquenium, we propose a translational programme that aims to develop the next generation of imaging approaches for investigation of disease biology in humans based on metabolism. Imaging using positron emission tomography (PET) remains one of the most direct ways of interrogating molecular mechanisms derailed in many diseases including cancer. PET methods are non-destructive and allow tissue biology to be investigated in the species of interest - the human being - non-invasively without associated sampling errors or tissue alterations that occur with biopsy-based approaches. Availability of appropriate probes and their validation in humans remains the major bottleneck in this field of research. Using cancer as the model, we have over the past five years advanced new probes for PET into human imaging to allow associated molecular mechanisms to be investigated. Of current interest is how tumours reprogramme their metabolism, which is difficult to measure by traditional methods in living organs and tissues. In the coming 5 years we will introduce two new imaging probes into humans and complete work on another. These probes detect how tissues burn fatty acids, store energy in the form of glycogen and make synthesise the precursors for membranes. The connectivity of this programme - chemistry design, automation, regulatory, mathematical modelling, and comparing imaging output to pathology - will allow us to provide the tools for translating our post-genome understanding of reprogrammed tumour metabolism into scientific investigation of diseased tissues in situ in humans, while developing candidate probes with potential for managing patients.
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