| Literature DB >> 26825776 |
Louise M Jørgensen1,2, Pia Weikop3,4, Jonas Villadsen1, Tanel Visnapuu3,5, Anders Ettrup1, Hanne D Hansen1, Anders O Baandrup6, Flemming L Andersen7, Carsten R Bjarkam8, Carsten Thomsen2,9, Bo Jespersen10, Gitte M Knudsen1,2.
Abstract
Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [11C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular 5-HT levels with microdialysis and [11C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2-11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in [11C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [11C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.Entities:
Keywords: 5-HT; Positron emission tomography; brain imaging; kinetic modelling; neurosurgery
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Year: 2016 PMID： 26825776 PMCID： PMC5381441 DOI： 10.1177/0271678X16629483
Source DB: PubMed Journal: J Cereb Blood Flow Metab ISSN： 0271-678X Impact factor: 6.200