Cambridge PET Neurochemist Training Programme

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 Alzheimer?s disease, depression, schizophrenia, obsessive compulsive disorder and drug addiction.

To address one of the major restrictions on the use of the molecular imaging technique of positron emission tomography (PET) for neuroscience research at Cambridge, the lack of trained PET chemists 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 US and Europe 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 yours. Integrated with this training, is the development of probes for the 5-HT2a receptors and beta-amyloid plaques and in the second phase of the programme collaboration with Siemens in the development of novel imaging probes for neurofibrillary tangles, one of the main neuropathological features of Alzheimer s disease (AD) and other dementias.
The tracers will then be applied to PET imaging projects in the area of neuropsychiatric and neurodegenerative disorders, with a focus on 1) preclinical studies that have significant translational aspects and 2) human research projects targeted toward understanding the mechanisms of neurological diseases and thereby identifying potential therapeutics. The proposed projects include; i) studies on impulsivity based on imaging 5-HT2a receptors on rats with this behavioural trait; ii) imaging serotonergic modulation in marmosets to investigate mechanistic components common to various neuropsychiatric disorders such of schizophrenia, depression and obsessive compulsive disorder; iii) the role of 5-HT2a in frontotemporal dementia and iv) evaluation of the novel beta-amyloid tracer in AD and MCI patients and normal control subjects, coupled with autoradiographic experiments on brain tissue.