RT Journal Article
SR Electronic
T1 Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 460
OP 465
DO 10.2967/jnumed.113.125187
VO 55
IS 3
A1 Eriksson, Olof
A1 Selvaraju, Ram K.
A1 Johansson, Lars
A1 Eriksson, Jan W.
A1 Sundin, Anders
A1 Antoni, Gunnar
A1 Sörensen, Jens
A1 Eriksson, Barbro
A1 Korsgren, Olle
YR 2014
UL http://jnm.snmjournals.org/content/55/3/460.abstract
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.