NCT01778686

Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Gitte Moos Knudsen · Academic / Other
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Accepted

Summary

The purpose of this project was to introduce the recently developed positron emission tomography (PET) tracer \[11C\]Cimbi-36 for use in clinical studies and to investigate the ability of the tracer to quantify the 5-HT2A receptor in the human brain. As a receptor agonist, \[11C\]Cimbi-36 binding will provide a more functional picture of 5-HT2A receptors, while this binding is thought to be correlated to brain serotonin levels. Both measurement of signaling through the 5-HT2A receptor and measurement of serotonin levels in vivo would have great scientific relevance for significant diseases such as depression and schizophrenia.

Detailed description

The serotonin 2A (5-HT2A) receptor is the most abundant excitatory serotonin (5-HT, 5-hydroxytryptamine) receptor in the human brain, and multiple positron emission tomography (PET) studies have investigated the 5-HT2A receptors in the human brain using antagonist radioligands. However, the currently available antagonist PET radioligands bind the total pool of 5-HT2A receptor receptors whereas a 5-HT2A receptor agonist binds the high-affinity subgroup of the receptors which are also G-protein coupled, and thus hypothesized to be the functional relevant population of receptors. At the Center for Integrated Molecular Brain Imaging (CIMBI), a novel agonist PET radioligands for brain imaging of 5-HT2A receptors was recently validated in animals (Ettrup et al. 2011, EJNMMI). In the human brain, \[11C\]Cimbi-36 was validated as a selective 5-HT2A receptor agonist PET radioligand through a blocking study with the 5-HT2A receptor antagonist pharmaceutical ketanserin. In this validation study, the biodistribution and kinetic modelling of \[11C\]Cimbi-36 binding in the human brain was also validated. With these studies, investigators will test the most promising of these, \[11C\]Cimbi-36, in clinical trials, where it will provide a novel method for detecting dysfunction in the 5-HT system. The specific aim of this clinical trial is: \- To examine the effect of acute alterations in 5-HT levels on cerebral \[11C\]Cimbi-36 binding in healthy volunteers who will be PET-scanned at baseline and after pharmacological or dietary interventions that either increase or decrease cerebral 5-HT levels. It is hypothesized that this novel agonist radioligand will provide both a more physiological relevant measure of the 5-HT2A receptors and also reflect levels of cerebral 5-HT in humans, more specifically: BP will decrease after pindolol and selective serotonin reuptake inhibitor (SSRI) treatment and increase after acute tryptophan depletion (ATD). Placebo will leave binding potential (BP) unchanged.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	Citalopram and Pindolol	Citalopram: selective serotonin reuptake inhibitor Pindolol: non-selective beta blocker and 5-HT1A receptor antagonist
OTHER	Placebo	On the second PET scanning day, subjects received a protein drink as well as a 50 ml saline infusion over 1 hour starting 30 min before PET scanning.
DIETARY_SUPPLEMENT	Acute tryptophan depletion

Timeline

• Start date: 2013-01-01
• Primary completion: 2013-11-01
• Completion: 2013-11-01
• First posted: 2013-01-29
• Last updated: 2025-02-20
• Results posted: 2024-10-09

Locations

1 site across 1 country: Denmark