PET-imaging in depression and antidepressant therapies : focus on the serotonin system and the cerebral glucose metabolism

The main scope of the research summarised in this dissertation comprises the use of positron emission tomography to investigate the role of the serotonin transporter in depression and antidepressant therapies. Hereby, several studies were performed using the PET radiotracer [11C]DASB, which specifically targets the serotonin transporter. To allow qualitative and safe research with this radiotracer, the first research topic focussed on the optimization of the radiotracer’s purification procedure and its quality control. Using this radiotracer, a first-in-dog study was carried out to investigate the radiotracer’s distribution and to define the appropriate image quantification methods. Subsequently, this radiotracer was used to perform a dose-occupancy in the dog to estimate the optimal dosing regimen to treat dogs with behavioural disorders with escitalopram. A second part of the dissertation focuses on rats and the current position of repetitive transcranial magnetic stimulation (rTMS) in the rat. Hereby, several additional objectives were put forward. The first objective comprised the evaluation of the accuracy of a for rodents adapted human neuronavigation system to perform rTMS in the rat. A second objective was the investigation of the construct validity of two depression models in terms of altered regional glucose metabolism. This was investigated via a PET study using the radiotracer [18F]FDG. Finally, for the preferred depression model, which was the one based on chronic corticosterone injections, the scope was extended from the serotonin transporter to the serotonin 5-HT1A and 5-HT2A receptors to explore the role of the serotonin system in the pathophysiology of this depression model in the rat. For this purpose, three radiotracers were applied: [11C]DASB, [18F]MPPF, and [18F]altanserin. This allowed to image the serotonin transporters, the 5-HT1A receptors, and the 5-HT2A receptors, respectively.