Disturbances in the serotonin (5-HT) transmitter system are seen in many neuropsychiatric disorders and brain disorders cause approximately one-third of the burden of illness in Europe. The aim of our proposal is to develop tools for in vivo imaging of the human brain with particular focus on the 5-HT7 and the 5-HT2A receptor. Both the 5-HT7 and 5-HT2A receptors are recognised as being involved in the pathophysiology of brain disorders and are also important drug targets.
Today, no suitable PET radiotracer exists for 5-HT7 receptor brain imaging, but access to such a radiotracer would enable new groundbreaking discoveries in human brain disorders. It would also allow the pharmaceutical industry to assess their compounds’ blood-brain barrier penetration and receptor occupancy in humans prior to clinical trials and thereby importantly guide the choice of drug dose. With the development of our promising 5-HT2A receptor agonist [11C]Cimbi-36 we will explore the exciting prospects of its ability to image the brain’s own 5-HT release under pharmacological and functional challenges. Our last goal is to develop a general method for 18F-labelling of aromatic rings that could expand the possibilities for 18-F radiolabelling with this longer-lived radioisotope and thereby enable dissemination throughout Europe to complete, e.g. multi-center studies with productions in a few European centres.
On a world-wide scale, there is a severe shortage of skilled and experienced PET radiochemists. The steeply increasing numbers of PET centres throughout Europe has generated an urgent and unmet need for the type of cross-disciplinary skills that will be provided through the planned training programme.
The project has been initiated and the concepts tested over the last 9 months. This has enabled us to improve the research project further and to develop a pertinent contingency plan. Thus, we find that the timing to carry out the project is just right now.
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