Serotonin 2A Receptor Agonist Binding in the Human Brain with [11C]Cimbi-36
Journal of Cerebral Blood Flow & Metabolism – April 30, 2014
Source: OpenAlex
Summary
A groundbreaking radioligand, [11C]Cimbi-36, has for the first time successfully imaged serotonin 2A (5-HT2A) receptors in the human brain. This novel serotonin agonist offers a direct measure of receptor activity. Utilizing medical imaging techniques, high brain uptake was observed in 29 healthy volunteers. Further, in 5 subjects, a chemical blocking agent significantly decreased binding, confirming its precise interaction with the 5-HT2A receptor. This advancement in chemistry and neuroscience provides an unprecedented tool to understand serotonin's role in brain function.
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 [ 11 C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT 2A receptors with [ 11 C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [ 11 C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [ 11 C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT 2A receptor antagonist ketanserin before a second PET scan significantly decreased [ 11 C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [ 11 C]Cimbi-36 binding is selective for 5-HT 2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT 2A receptors in the human brain. Thus, we here describe [ 11 C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT 2A receptors in the human brain.