Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors
Status:
Completed
Trial end date:
2013-11-01
Target enrollment:
Participant gender:
Summary
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.