[F]F13640, a 5-HT Receptor Radiopharmaceutical Sensitive to Brain Serotonin Fluctuations.

Introduction: Serotonin is involved in a variety of physiological functions and brain disorders. In this context, efforts have been made to investigate the fluctuations of this neurotransmitter using positron emission tomography (PET) imaging paradigms. Since serotonin is a full agonist, it binds preferentially to G-protein coupled receptors.

Preclinical validation of [F]2FNQ1P as a specific PET radiotracer of 5-HT receptors in rat, pig, non-human primate and human brain tissue.

Introduction: The aim of this study was to perform in-vitro and in-vivo radiopharmacological characterizations of [F]2FNQ1P, a new PET radiotracer of 5-HT receptors, in rat, pig, non-human primate and human tissues. The 5-HT receptor is one of the more recently identified serotonin receptors in central nervous system and, because of its role in memory and cognitive processes, is considered as a promising therapeutic target.

Methods: In-vitro autoradiography and saturation binding assays were performed in postmortem brain tissues from rat, pig, non-human primate and human caudate nucleus, completed by serum stability assessment in all species and cerebral radiometabolite and biodistribution studies in rat.

Serotonin 5-HT Receptor Biased Agonists Induce Different Cerebral Metabolic Responses: A [F]-Fluorodesoxyglucose Positron Emission Tomography Study in Conscious and Anesthetized Rats.

Serotonin 5-HT receptors constitute an attractive therapeutic target for various psychiatric or neurodegenerative disorders. These receptors are expressed in multiple brain regions on different neuronal populations and can be coupled with distinct G-protein subtypes; such functional diversity complicates the use of 5-HT ligands in several pathologies where it would be desirable to stimulate the receptors in a precise region. Therefore, using "biased agonists" able to target specifically certain subpopulations of 5-HT receptors would enable achievement of better therapeutic benefit.

In vivo biased agonism at 5-HT receptors: characterisation by simultaneous PET/MR imaging.

In neuropharmacology, the recent concept of 'biased agonism' denotes the capacity of certain agonists to target-specific intracellular pathways of a given receptor in specific brain areas. In the context of serotonin pharmacotherapy, 5-HT receptor-biased agonists could be of great interest in several neuropsychiatric disorders. The aim of this study was to determine whether biased agonists could be differentiated in terms of regional targeting by use of simultaneous functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) brain imaging.

F-F13640 preclinical evaluation in rodent, cat and primate as a 5-HT receptor agonist for PET neuroimaging.

Serotonin 1A receptors are known to play an important role in many psychiatric and neurodegenerative disorders. Currently, all available 5-HT receptor PET radiopharmaceuticals that are radiolabeled with fluorine-18 are antagonists. As agonists bind preferentially to the high-affinity state of receptors, it would be of great interest to develop agonist radioligands which could provide a measure of the functional 5-HT receptors in pathophysiological processes.