Localization of serotonin 5‐HT2 receptors in living human brain by positron emission tomography using N1‐([11C]‐methyl)‐2‐BR‐LSD
Synapse – January 01, 1987
Source: OpenAlex
Summary
The innovative radioligand N1‐([11C]‐Methyl)‐2‐Br‐LSD ([11C]‐MBL) demonstrates high-affinity binding to serotonin 5-HT2 receptors, with a binding potential of 0.5 nM. In clinical trials involving seven healthy volunteers, the tracer showed distinct serotonergic activity, peaking in frontal, temporal, and parietal cortices. Notably, the frontal cortex-to-cerebellum ratios varied from 1.7 to 2.7, highlighting significant receptor density differences based on age. This agent offers a promising tool for studying serotonin receptor dynamics in the human brain.
Abstract
Abstract 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.