Serotonin 2A Receptor Agonist Binding in the Human Brain with [11C]Cimbi-36
Anders Ettrup, Sofi Da Cunha‐bang, Brenda Mcmahon, Szabolcs Lehel, Agnete Dyssegaard, Anine W Skibsted, Louise Møller Jørgensen, Martin Hansen, Anders Ohlhues Baandrup, Søren Bache, Claus Svarer, Jesper L. Kristensen, Nie Gillings, Jacob Madsen, Gitte M. Knudsen
Journal of Cerebral Blood Flow & Metabolism April 30, 2014 DOI: 10.1038/jcbfm.2014.68 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | First-in-human clinical trial Peer reviewed |
|---|---|
| Sample size | 29 |
| Population | Healthy volunteers |
| Intervention | ketanserin |
| Topics | Serotonin |
| Keywords | Serotonin agonist Human brain 5-HT Receptor Endocrinology 14-3-3 protein interactions |
| Citations | 106 |
| Key findings | [11C]Cimbi-36 is the first agonist PET radioligand to successfully image and quantify 5-HT2A receptors in the human brain. |
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.
Comparable studies
Other non-randomized and open-label trials on serotonin, most cited first.
Citations in the library
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- Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Current Biology September 27, 2018
- The promises and perils of psychedelic pharmacology for psychiatry. Nature Reviews Drug Discovery June 1, 2022
- A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding European Neuropsychopharmacology March 4, 2020
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