No abstract

[ 11 C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT 2A ) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with INTRODUCTIONThe neurotransmitter serotonin (5-HT) is a modulator of a vast variety of normal physiologic effects and is also involved in the pathophysiology of central nervous system disorders such as depression and schizophrenia. The serotonin 2A (5-HT 2A ) receptor is the main excitatory 5-HT receptor in the human central nervous system, it is responsible for the hallucinogenic effects of recreational agonist drugs such as lysergic acid diethylamide and psilocybin, and 5-HT 2A receptor antagonism is a characteristic of atypical antipsychotics. 1 Furthermore, changes in 5-HT 2A receptor levels have been linked to the pathophysiology of human diseases such as depression. 2,3 Positron emission tomography (PET) has unsurpassed sensitivity and selectivity to detect and quantify specific proteins and processes in the human brain. Positron emission tomography imaging with radioligands is a widely used tool to quantify differences in receptor binding, for example, between patient and control groups, to quantify receptor occupancy of pharmacological interventions or to measure neurotransmitter release in vivo. 4,5 In clinical studies, 5-HT 2A receptor antagonists have for decades been in use as PET radioligands, most notably [ 18 F]altanserin and [ 11 C]MDL100907. 6 However, agonist PET radioligands may functionally possess several advantages over antagonists. Importantly, agonist radioligands in the dopamine system have an increased sensitivity to endogenously released neurotransmitter. Here, several studies using pharmacologically increased dopamine

No abstract