Multi-user microPET/CT equipment for biomedical research

Positron emission tomography (PET) combined with X-ray computed tomography (PET/CT) is an imaging technique that is commonly used in patients for diagnosing disease (often cancer, but also heavily used in other indications such as cardiology and neuroscience) as well as measuring responses to treatment and checking to see if disease has recurred. PET/CT can also be used in small animals (in this case rodents) using specialist, much smaller scanners (microPET/CT). This allows researchers to visualise radioactive substances that are designed to localise at specific sites in the body, for instance areas of cancer, inflammation or tissue damage. Thus PET/CT imaging is extremely useful in accelerating the development of new drugs or therapeutic approaches. Using this microPET/CT equipment we will work to develop ways of tracking and quantifying advanced cell therapies. These are immune cells that are taken from the patient, modified in a laboratory so that they can better target cancer cells and then reinjected into the patient where they kill the cancer cells. In our research project we will modify the cells so that when they are injected into animals, not only do they target the tumours, they also become visible when the animal is injected with a specific radioactive substance and scanned in the microPET/CT camera. This allows us to track the cells in live animals to obtain information about where the cells go in the body, how many of them survive and proliferate and for how long. Although we have been able to do this with existing equipment, the new microPET/CT has much higher quantitative accuracy, sensitivity and resolution which will accelerate this research in solid tumours which are difficult to treat with this approach. We hope to find ways of better targeting tumours and test strategies to circumvent the difficulties of the cells accessing solid tumours such as osteosarcoma in children and adolescents and neuroblastoma in children. In other work, we will characterise new mouse models of cancer that are designed to give insight into how lung cancer develops so as to find new ways of treating it. Using the equipment to image the response to therapy will allow the development of new therapy combinations such as radiation, chemotherapy and antibody therapy in animals that have normal immune responses. In drug development work, we will develop new radioactive diagnostic imaging agents for screening patients to see if they are likely to respond to targeted therapies. Other researchers developing treatments for spinal cord and traumatic brain injury will use this equipment to look at response to neuroprotective agents as well as those researching the pregnancy complication, pre-eclampsia. This versatile piece of equipment will provide valuable data in a range of existing and future research projects, pushing forward knowledge in the different fields to inform clinical trials in development.

Positron emission tomography (PET) combined with X-ray CT in small animals (microPET/CT) is one of the workhorses of translational science, allowing testing of scientific hypotheses in a whole body approach and accelerating the drug development process. Although much ground-breaking work can be carried out in vitro and in silico, many investigations benefit greatly from characterisation and validation in whole body in vivo models. These range from basic biology investigations of physiological processes in disease and normal development, tissue/disease in vivo targeting and pharmacokinetic studies, testing new therapy combinations in the context of an intact immune system through to quantitative studies of response markers to therapy.
This new microPET/CT imaging system will allow us to carry out a mixture of basic and translational science with greatly improved resolution, throughput, sensitivity and quantitative accuracy. The areas of research which will benefit range from the characterisation of new, more clinically relevant genetically modified mouse models of lung cancer, the effect of vascular modulation agents on tumour cell hypoxia and metabolism, understanding the effect of the maternal immune system on cardiac outcomes in pre-eclampsia, development of precision medicines through targeting and validation of theranostic pairs, quantitative visualisation of prognostically-relevant tumour characteristics to allow stratification for treatment, mitigating the impact of traumatic brain injury, to development of methods to quantify genetically modified cell therapies for solid tumours, including in children. Outcomes will be mainly in understanding mechanisms of disease to be able to develop appropriate therapeutic strategies and in optimising therapies and therapeutic approaches for clinical translation.