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Serotonin synthesis studied with positron emission tomography (PET)
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK 2100, Denmark.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. National Board of Health and Welfare, Stockholm, 106 30, Sweden.
2014 (English)In: PET and SPECT of Neurobiological Systems / [ed] Rudi A.J.O. Dierckx, Andreas Otte, Erik F.J. de Vries, Aren van Waarde & Paul G.M. Luiten, Springer Berlin/Heidelberg, 2014, 687-709 p.Chapter in book (Other academic)
Abstract [en]

Positron emission tomography (PET) has the potential to study the biosynthesis and release of serotonin (5HT) at brain serotonergic neurons. PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes. This section focuses on probes to measure seroonin synthesis rate. Knowledge of altered 5HT synthesis and release in disease states may furnish basis for effective pharmacotherapy that may improve the care of psychiatric and neurological disease. Validation of PET measurements of the two PET tracers using perturbation showed that 5-hydroxy-L-(beta-11C tryptophan) (5HTP) quantifies the activity of amino acid decarboxylase in the conversion to 5HT. On the other hand, alpha-methyl-tryptophan (AMT) measures the conversion to the corresponding 5-hydroxytryptophan analogue. The irreversible binding of the PET probe 5HTP in the monkey brain was lower in the presence of NSD1015 which was used to inhibit the decarboxylation step in 5HT synthesis. 5HTP seems thus to have potential for tracking changes in the activity of the biosynthesis enzyme. In contrast, the accumulation of 5HTP was unaffected by clorgyline used to inhibit the metabolism of the probe in the brain. This indicates that on a PET timescale, elimination of the main metabolite from the brain is negligible and would not alter calculation of 5HTP transfer to 5HT. The extent and distribution of irreversible binding of a substrate for the first enzyme in 5HT formation alpha-methyltryptophan AMT were different from those of 5HTP, suggesting that the two PET probes provide estimates related to the enzyme activity of different steps in the 5HT synthesis pathway. Applications of the two tracers HTP and AMT are reviewed. Up to now, 5HTP has mainly been used for the detection, staging and treatment evaluations of neuroendocrine tumours. Though, a few studies using 5HT have been conducted on CNS disorders. AMT-PET studies have mainly been confined to brain diseases causing various degree of neurodegeneration.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2014. 687-709 p.
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-309394DOI: 10.1007/978-3-642-42014-6_24ScopusID: 2-s2.0-84955571976ISBN: 9783642420146 (print)ISBN: 9783642420139 (print)OAI: oai:DiVA.org:uu-309394DiVA: diva2:1054623
Available from: 2016-12-08 Created: 2016-12-02 Last updated: 2016-12-08Bibliographically approved

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