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Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
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2014 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, no 3, 460-465 p.Article in journal (Refereed) Published
Abstract [en]

Serotonergic biosynthesis in the endocrine pancreas, of which the islets of Langerhans is the major constituent, has been implicated in insulin release and β cell proliferation. In this study, we investigated the feasibility of quantitative noninvasive imaging of the serotonergic metabolism in the pancreas using the PET tracer (11)C-5-hydroxy-l-tryptophan ((11)C-5-HTP).

METHODS: Uptake of (11)C-5-HTP, and its specificity for key enzymes in the serotonergic metabolic pathway, was assessed in vitro (INS-1 and PANC1 cells and human islet and exocrine preparations) and in vivo (nonhuman primates and healthy and diabetic rats).

RESULTS: In vitro tracer uptake in endocrine cells (INS-1 and human islets), but not PANC1 and exocrine cells, was mediated specifically by intracellular conversion into serotonin. Pancreatic uptake of (11)C-5-HTP in nonhuman primates was markedly decreased by inhibition of the enzyme dopa decarboxylase, which converts (11)C-5-HTP to (11)C-serotonin and increased after inhibition of monoamine oxidase-A, the main enzyme responsible for serotonin degradation. Uptake in the rat pancreas was similarly modulated by inhibition of monoamine oxidase-A and was reduced in animals with induced diabetes.

CONCLUSION: The PET tracer (11)C-5-HTP can be used for quantitative imaging of the serotonergic system in the endocrine pancreas.

Place, publisher, year, edition, pages
2014. Vol. 55, no 3, 460-465 p.
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Basic Medicine
Identifiers
URN: urn:nbn:se:uu:diva-218878DOI: 10.2967/jnumed.113.125187ISI: 000332352100028PubMedID: 24525204OAI: oai:DiVA.org:uu-218878DiVA: diva2:697701
Available from: 2014-02-19 Created: 2014-02-19 Last updated: 2017-12-06Bibliographically approved

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Eriksson, OlofSelvaraju, Ram KJohansson, LarsEriksson, Jan WSundin, AndersAntoni, GunnarSörensen, JensEriksson, BarbroKorsgren, Olle

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Eriksson, OlofSelvaraju, Ram KJohansson, LarsEriksson, Jan WSundin, AndersAntoni, GunnarSörensen, JensEriksson, BarbroKorsgren, Olle
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Preclinical PET PlatformRadiologyClinical diabetology and metabolismOncologySection of Nuclear Medicine and PETEndocrine Tumor BiologyClinical Immunology
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