Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-52644
Quednow, B B; Treyer, V; Hasler, F; Dörig, N; Wyss, M T; Burger, C; Rentsch, K M; Westera, G; Schubiger, P A; Buck, A; Vollenweider, F X (2012). Assessment of serotonin release capacity in the human brain using dexfenfluramine challenge and [(18)F]altanserin positron emission tomography. NeuroImage, 59(4):3922-3932.
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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 40mg (n=6) or 60mg (n=7) of the potent 5-HT releaser dexfenfluramine separated by an interval of 14days. Three further subjects received placebo on both days. Two hours after placebo/drug administration, 250MBq 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 90min. 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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry|
04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Affective Disorders and General Psychiatry Zurich East
04 Faculty of Medicine > Neuroscience Center Zurich
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||19 Dec 2011 13:10|
|Last Modified:||14 Dec 2012 12:10|
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