MICA: Training and Novel Probes Programme in PET Neurochemistry - PET Call

Some radioactive molecules emit gamma radiation that can be detected outside the body and so when injected into humans and animals, in safe low levels, can be used to generate images, using sophisticated scanners, of the brain for biomedical research and clinical diagnosis. However, the molecules have to be designed to target the sites of the brain to be investigated, which is done by attaching a biological compound to the radioactive molecule to create products called radiopharmaceuticals. Due to the severe lack of scientists in the UK who have the specialised skills to design and prepare these radiopharmaceuticals we plan to recruit and train a scientist to join our multidisplicinary team. To achieve this we have created a bespoke training programme which will involve learning from researchers in academia and industry, who are either developing and/or using this imaging technology. As part of this training the scientist will help design new radiopharmaceuticals that would then be used in our on-going research programmes to understand the biological mechanisms of some major diseases and disorders of the brain, and thereby identify some possible treatments. For this specific programme we would be undertaking research projects on traumatic brain injury, depression, schizophrenia, obsessive compulsive disorder and drug addiction.

Technical Summary
To address one of the major restrictions in the use of the molecular imaging technique of positron emission tomography (PET) for neuroscience research at Cambridge, the lack of trained PET chemist to design and prepare the required brain imaging probes, proposed is an integrated programme of training and research. In partnership with PET centres, academic and industrial, in the UK and US we have constructed a training programme designed to train a post-doctoral scientist with a PhD background in chemistry to "group leader" capability within four years. Integrated with this training, is, i) the implementation a radioligand for mGluR5 receptors which will applied in our preclinical programme to understand the role of these receptors in neuropsychiatric disorders such as depression, obsessive compulsive disorder (OCD), drug addiction and schizophrenia, and ii) in collaboration with GE Healthcare to implement a NMDA radioligand to be applied in clinical studies on traumatic brain injury. In the later stages of the programme the trainee will focus on development of novel imaging probes for imaging the tropomyosin-related kinase receptor B for future application in neuropsychiatric research.

The impact of this project and the beneficiaries are in two main areas:

Health and Well being: The overarching aim of our programmes of research is to improve health and well-being of the UK population that are affected by the various disease and disorders that are outlined in this proposal. These include traumatic brain injury (TBI), schizophrenia, obsessive-compulsive disorder (OCD), anxiety, depression and autism. A range of neurological disorders that can result in death, severe and permanent disability, neurocognitive and neuropsychiatric deficits. Our objectives are to understand the mechanisms and pathophysiology of these disorders and thereby develop effective treatments and therapies. Therefore, the immediate beneficiaries of our research outcomes will be these patients. Indirectly their families, who often carry major burden of care, will benefit and the general population through a reduction in the substantial NHS and social service budgets that arise from these disorders. Savings that would be of benefit to the nation's general economy. The projects outlined in this proposal are consistent with our overall objectives, with the immediate aim to train much need staff to extend the use of a powerful technology that will greatly enhance and facilitate these on-going programmes of research. Due to the close relationship between the University of Cambridge and Addenbrooke's hospital enabled by being a Comprehensive Biomedical Centre, and collectively with the Cambridgeshire Mental Health Trust and the Cambridgeshire Primary Care Trust been awarded Academic Health Sciences Centre status the research outcomes of the project can be immediately applied to inform clinical decisions on these patients. Therefore our research project will be of benefit to the clinical staff responsible for the care of these patients.

Related to clinical care, diagnostic services will benefit from the development and validation of the novel PET radiotracers we plan to develop, in particular fluorine-18 radioligands, which are appropriate for clinical imaging services. These novel radiotracers will be of significant additions to the growing field of molecular imaging, which can help in early diagnosis of disease, clinical characterisation and evaluation of subsequent treatment.

Wealth creation and prosperity: The development of a validated PET radioligand would be of commercial interest to the radiopharmaceutical companies e.g. GE healthcare and Siemens who have established manufacturing sites in the UK to underpin the increasing use of PET diagnostic service in the NHS. We would exploit the commercial potential of our novel radiotracers to the financial benefit of both the university and the radiopharmaceuticals company, through partnership.

The UK pharmaceutical industry could also benefit from the outcome of these projects in several forms. With the specific difficulty of developing drugs for neurological disorders, increased understanding of these pathologies will help to develop more effective drugs, while the availability of validated PET radioligands would be a powerful tool for clinical trials on novel drugs, e.g. to determine receptor occupancy and additional pharmacokinetic and pharmacodynamic data.