Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas

Journal of Nuclear Medicine

Jan W. Eriksson¹  Gunnar Antoni¹  Barbro Eriksson¹  Olof Eriksson¹  Jens Sörensen¹  Lars Johansson¹  Anders Sundin¹  Ram K. Selvaraju¹  Olle Korsgren¹ 

关键词: 5-hydroxy tryptophan;    serotonin biosynthesis;    beta cell imaging;    diabetes;   

DOI  :  10.2967/jnumed.113.125187

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 11C-5-hydroxy-l-tryptophan (11C-5-HTP). Methods: Uptake of 11C-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 11C-5-HTP in nonhuman primates was markedly decreased by inhibition of the enzyme dopa decarboxylase, which converts 11C-5-HTP to 11C-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 11C-5-HTP can be used for quantitative imaging of the serotonergic system in the endocrine pancreas.

【 授权许可】

Unknown