Assessment of serotonin release capacity in the human brain using dexfenfluramine challenge and [18F]altanserin positron emission tomography

Autor: Boris B. Quednow, Gerrit Westera, Matthias T. Wyss, Alfred Buck, Nadja Dörig, Cyrill Burger, Felix Hasler, Franz X. Vollenweider, Katharina Rentsch, Valerie Treyer, Pius A. Schubiger
Přispěvatelé: University of Zurich, Quednow, Boris B
Rok vydání: 2012
Předmět:
2805 Cognitive Neuroscience
Adult
Male
Fluorine Radioisotopes
Serotonin
medicine.medical_specialty
Cognitive Neuroscience
610 Medicine & health
Young Adult
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Bolus (medicine)
Dexfenfluramine
Double-Blind Method
Internal medicine
540 Chemistry
medicine
Humans
10064 Neuroscience Center Zurich
5-HT receptor
10038 Institute of Clinical Chemistry
030304 developmental biology
0303 health sciences
Brain
10181 Clinic for Nuclear Medicine
Human brain
Prolactin
Logan plot
Serotonin Receptor Agonists
3. Good health
medicine.anatomical_structure
Endocrinology
Neurology
chemistry
10054 Clinic for Psychiatry
Psychotherapy
and Psychosomatics
10076 Center for Integrative Human Physiology
2808 Neurology
Positron-Emission Tomography
Altanserin
570 Life sciences
biology
Ketanserin
030217 neurology & neurosurgery
medicine.drug
Zdroj: NeuroImage
ISSN: 1053-8119
DOI: 10.1016/j.neuroimage.2011.09.045
Popis: Although alterations of serotonin (5-HT) system functioning have been proposed for a variety of psychiatric disorders, a direct method quantitatively assessing 5-HT release capacity in the living human brain is still lacking. Therefore, we evaluated a novel method to assess 5-HT release capacity in vivo using dexfenfluramine challenge and [(18)F]altanserin positron emission tomography (PET). Thirteen healthy male subjects received placebo and single oral doses of 40 mg (n = 6) or 60 mg (n = 7) of the potent 5-HT releaser dexfenfluramine separated by an interval of 14 days. Three further subjects received placebo on both days. Two hours after placebo/drug administration, 250 MBq of the 5-HT(2A) receptor selective PET-radiotracer [(18)F]altanserin was administered intravenously as a 30s bolus. Dynamic PET data were subsequently acquired over 90 min. Moreover, arterial blood samples were drawn for measurement of total activity and metabolite correction of the input function. Dexfenfluramine as well as cortisol and prolactin plasma concentration-time profiles was quantitatively determined. Tracer distribution volumes for five volumes-of-interest (prefrontal and occipital cortex, insula, thalamus, caudatum) were calculated by the Logan plot and a 2-tissue compartment model. Dexfenfluramine dose-dependently decreased the total distribution volume of [(18)F]altanserin in cortical regions independent of the PET modeling approach. Cortisol and prolactin plasma concentrations were dose-dependently increased by dexfenfluramine. The decrease in cortical [(18)F]altanserin receptor binding under dexfenfluramine was correlated with the increase of plasma prolactin. These data suggest that the combination of a dexfenfluramine-induced 5-HT release and subsequent assessment of 5-HT(2A) receptor availability with [(18)F]altanserin PET is suitable to measure cortical 5-HT release capacity in the human brain.
Databáze: OpenAIRE
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