Serotonin (5-hydroxytryptamine, 5-HT) has diverse physiologic roles as a 
neurotransmitter in the central nervous system (1). It is involved in regulation 
and modulation of sleep, affective and personality behaviors, and pain. It also 
is a regulator of smooth muscle function and platelet aggregation. The brain 
cortical 5-HT system has been implicated in several neuropsychiatric disorders, 
including major depression, anxiety, obsessive-compulsive disorder, and 
schizophrenia (2, 3). The effects of 5-HT are mediated by as many as seven 
classes of receptor populations (5-HT1 to 5-HT7), many of which include several 
subtypes (4). There are three receptor subtypes within the G protein-coupled 
5-HT2 receptor family: 5-HT2A, 5-HT2B, and 5-HT2C. 5-HT2A receptors are 
abundantly present in the cerebral cortex, basal forebrain, hippocampus, 
amygdala, dorsal thalamus, hypothalamus, superior colliculus, substantia nigra, 
pedunculopontine nucleus, legmental area, and myelencephalon (5). 5-HT2A 
receptors are involved in mediation of normal and psychotic states, working 
memory, regulation of GABAergic and cholinergic neuronal cells, sleep, 
peripheral pain, and cardiovascular functions. 5-HT2B receptors are found mainly 
in several peripheral tissues, such as the stomach, intestine, and pulmonary 
smooth muscle, and in the myocardium. In the brain, 5-HT2B receptors are found 
in discrete nuclei of the cerebellum, lateral septum, dorsal hypothalamus, 
dorsal raphe, and amygdala. 5-HT2C receptors are found in the choroid plexus, 
substantia nigra, globus pallidus, and ventromedial thalamus. 5-HT2A receptors 
are implicated in several psychiatric disorders, such as schizophrenia, 
depression, and obsessive-compulsive disorder. Thus, there is a need for 
selective ligands to investigate the pharmacologic role of 5-HT2A receptors. 
There have been several studies to develop specific 5-HT2A radioligands, such as 
[11C]ketanserin (6), [18F]spiperone (7), [11C]methylspiperone ([11C]NMSP), and 
[18F]setoperone [PubMed], for positron emission tomography (PET) imaging. 
However, none has proven specific for 5-HT2A receptors because these compounds 
also bind to other receptors, such as dopamine receptors and 5-HT1 receptor 
subtypes. Altanserin, a fluorobenzoyl derivative related to ketanserin, was 
reported to be a potent inhibitor of 5-HT2A receptors with >100-fold selectivity 
over D2/3 receptors, 5-HT1A, 5-HT6, and 5-HT7 (8, 9). This led to the 
development of 
3-[2-[4-(4-[18F]fluorobenzoyl)-1-piperidyl]ethyl]-2-sulfanyl-3H-quinazolin-4-one 
([18F]altanserin) as a useful tool for 5-HT2A receptor PET imaging in vivo (10).