Work package leader: Hanne D. Hansen, NRU
In non-human primates (NHPs), we have previously found that targeted binding of an antagonist to dopamine D2 receptors elicits a hemodynamic response that is coupled to receptor occupancy. However, the hemodynamic response is not only dependent on receptor occupancy but also on the functionality of the drug, i.e. whether the drug is an agonist or an antagonist. Together with our collaborating partner at the Martinos Center in USA, we have shown that the 5-HT1BR partial agonist AZ10419369 elicited a dose-dependent biphasic hemodynamic response that was related to the 5-HT1BR occupancy. By contrast, injection of the antagonist GR127935 did not elicit significant hemodynamic responses, even at a 5-HT1BR cerebral occupancy similar to the one obtained with a high dose of AZ10419369. These results suggest that simultaneous PET-MRI opens for the possibility of testing novel drug compounds for their blood-brain-barrier passage, their brain occupancy and their functionality, based upon the hemodynamic response.
In our investigations of cerebral spatial and temporal response to triptans following experimental induction of migraine, we have completed the data collection and are now analysing the data. In this project, all patients have got three PET scans with 11C-AZ10419369: an interictal baseline scan and two scans after provocation of migraine.
Last but not least, we will settle a long-debated issue, namely to establish if migraine patients without aura (MO) symptoms have reduced brain serotonin levels. For this purpose, 16 MO patients will be scanned and compared to 16 matched healthy controls. The data collection and the data analysis is now finalized and a manuscript has been drafted of the results.