title: Quantitative imaging of serotonergic biosynthesis and degradation in the endocrine pancreas.
abstract: 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.
  
  
  CONCLUSIONS
  The PET tracer (11)C-5-HTP can be used for quantitative imaging of the serotonergic system in the endocrine pancreas.
authors: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden.
authors: Olof
authors: O
authors: Eriksson
authors: Ram K
authors: RK
authors: Selvaraju
authors: Lars
authors: L
authors: Johansson
authors: Jan W
authors: JW
authors: Eriksson
authors: Anders
authors: A
authors: Sundin
authors: Gunnar
authors: G
authors: Antoni
authors: Jens
authors: J
authors: Sörensen
authors: Barbro
authors: B
authors: Eriksson
authors: Olle
authors: O
authors: Korsgren
mesh_terms: D006916:5-Hydroxytryptophan; D000818:Animals; D002250:Carbon Radioisotopes; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis* / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D012701:Serotonin; D006916:5-Hydroxytryptophan; D008995:Monoamine Oxidase
keywords: 5-hydroxy tryptophan; beta cell imaging; diabetes; serotonin biosynthesis