PT  - JOURNAL ARTICLE
AU  - Olof Eriksson
AU  - Ram K. Selvaraju
AU  - Lars Johansson
AU  - Jan W. Eriksson
AU  - Anders Sundin
AU  - Gunnar Antoni
AU  - Jens Sörensen
AU  - Barbro Eriksson
AU  - Olle Korsgren
TI  - Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas
AID  - 10.2967/jnumed.113.125187
DP  - 2014 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 460--465
VI  - 55
IP  - 3
4099  - http://jnm.snmjournals.org/content/55/3/460.short
4100  - http://jnm.snmjournals.org/content/55/3/460.full
SO  - J Nucl Med2014 Mar 01; 55
AB  - 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.