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Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively capture temporal and spatial information about acute changes in brain neurotransmitter systems. We here evaluate the 5-HT 1B receptor partial agonist PET radioligand, [ 11 C]AZ10419369, for its sensitivity to detect changes in endogenous cerebral serotonin levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain serotonin levels, we compared the [ 11 C]AZ10419369 PET signal in the pig brain to simultaneous measurements of extracellular serotonin levels with microdialysis after various acute interventions (saline, escitalopram, fenfluramine). The interventions increased the cerebral extracellular serotonin levels to two to six times baseline, with fenfluramine being the most potent pharmacological enhancer of serotonin release. The interventions induced a varying degree of decline in [ 11 C]AZ10419369 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular serotonin level in the pig brain and the 5-HT 1B receptor occupancy indicates that [ 11 C]AZ10419369 binding is sensitive to changes in endogenous serotonin levels to a degree equivalent to that reported of [ 11 C]raclopride to dopamine, a much used approach to detect in vivo change in cerebral dopamine.

Cerebral serotonin release correlates with [11C]AZ10419369 PET measures of 5-HT1B receptor binding in the pig brain

Cerebral serotonin release correlates with [¹¹C]AZ10419369 PET measures of 5-HT_1B receptor binding in the pig brain