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Localization of serotonin 5‐HT 2 receptors in living human brain by positron emission tomography using N1‐([ 11 C]‐methyl)‐2‐BR‐LSD
Author(s) -
Wong Dean F.,
Lever John R.,
Hartig Paul R.,
Dannals Robert F.,
Villemagne Victor,
Hoffman Beth J.,
Wilson Alan A.,
Ravert Hayden T.,
Links Jonathan M.,
Scheffel Ursula,
Wagner Henry N.
Publication year - 1987
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890010502
Subject(s) - serotonin , ketanserin , serotonergic , receptor , radioligand , 5 ht receptor , putamen , human brain , chemistry , temporal cortex , medicine , binding potential , endocrinology , neuroscience , biology , biochemistry
N1‐([ 11 C]‐Methyl)‐2‐Br‐LSD ([ 11 C]‐MBL) has been developed as a positron emission tomography (PET) imaging agent for serotonin 5‐HT 2 receptors. In vitro receptor binding assays with nonradioactive MBL show high‐affinity binding to serotonin 5‐HT 2 receptors (K i = 0.5 nM), a secondary interaction of 8‐fold lower affinity with dopamine D 2 receptors, and low‐affinity interactions with α 1 ‐adrenergic as well as serotonin 5‐HT 1 receptors. Intravenous injection of [ 11 C]‐MBL in a baboon led to selective labeling of cortical regions that was markedly blocked by prior administration of ketanserin, a selective 5‐HT 2 receptor antagonist. Clinical trials with [ 11 C]‐MBL have been conducted in seven normal human volunteers, and the regional distribution of radioactivity in the brain was distinctly serotonergic. Labeling was highest in frontal, temporal, and parietal cortex with lower levels observed in caudate and putamen. The tracer rapidly washed from the cerebellum and the low levels of activity in this brain region were used to define nonspecific binding. The maximum specificity was reached between 30 and 60 minutes postinjection when frontal cortex to cerebellum ratios ranged from 1.7 for a 52‐year‐old male to 2.7 for a 30‐year‐old male. In agreement with previous studies, a trend towards lower ratios (lower serotonin 5‐HT 2 receptor levels) was observed in older volunteers. These studies indicate that [ 11 C]‐MBL is a selective radioligand that can be used to monitor serotonin 5‐HT 2 receptor densities in vivo in most regions of the human brain.