Research ArticleBasic Science Investigations

Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas

Olof Eriksson, Ram K. Selvaraju, Lars Johansson, Jan W. Eriksson, Anders Sundin, Gunnar Antoni, Jens Sörensen, Barbro Eriksson and Olle Korsgren
Journal of Nuclear Medicine March 2014, 55 (3) 460-465; DOI: https://doi.org/10.2967/jnumed.113.125187

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Figures

  • FIGURE 1.
    FIGURE 1.

    Immunohistochemical staining on serial sections of human pancreas was performed for insulin (A and C) and serotonin (B and D). Serotonin is localized in islets of Langerhans in nondiabetic subject (A and B) but not in islets of subject with longstanding T1D (C and D). Disappearance of serotonin is correlated with loss of insulin but not with glucagon.

  • FIGURE 2.
    FIGURE 2.

    (A) There is a strong linear correlation (R2 = 0.99, P < 0.05) between islet purity and 11C-5-HTP uptake in human islet preparations (n = 4). Extrapolation predicts low uptake in exocrine tissue and at least 15-fold increased uptake in islets. 11C-5-HTP uptake was partially inhibited by coincubation with DDC inhibitor carbidopa, confirming biosynthesis of 11C-serotonin in islets in vitro. 11C-5-HTP uptake in INS-1 cells (B), but not PANC1 (C), could be modulated by inhibition of DDC and MAO-A (stars indicate significance between clorgyline treatment, compared with baseline) or competition by unlabeled 5-HTP in excess.

  • FIGURE 3.
    FIGURE 3.

    PET measurements of 11C-5-HTP uptake in pancreas (A) of nonhuman primate are plotted over time. ● = 11C-5-HTP uptake in pancreas; ▪ = 11C-5-HTP uptake when administered together with carbidopa; and ○ = 11C-5-HTP uptake when administered together with clorgyline. 11C-5-HTP uptake in pancreas (as measured by AUC) was significantly decreased by intravenous preadministration of DDC inhibitor carbidopa or increased by intravenous preadministration of MAO-A-inhibitor clorgyline (B). Enhancement in hepatic uptake after administration of carbidopa (B) when compared with tracer alone is explained by increase in circulating amounts of 11C-5-HTP when administered together with carbidopa when compared with injection of tracer alone. (C and D) Abdominal HTP and PET/CT fusion images of nonhuman primate. Tracer uptake in pancreas (white arrow) is distinct (C), whereas no uptake is seen in nonendocrine organs such as spleen. Urinary excretion of tracer metabolites causes intense uptake in kidney pelvis (red arrow). Distinct pancreatic uptake is almost completely abolished by pretreatment by carbidopa (D).

  • FIGURE 4.
    FIGURE 4.

    Organ distribution after administration of 11C-5-HTP shows distinct uptake in pancreas, whereas tissues devoid of serotonergic enzymatic systems required for tracer metabolism (such as heart, liver, and muscle) show low accumulation 30 min after tracer administration (A). In diabetic animals, 11C-5-HTP uptake in pancreas is reduced 30 min after administration (A and B). Treatment with STZ induced progressive hyperglycemia through selective destruction of pancreatic β cells (C). In vivo 11C-5-HTP uptake in pancreas is significantly decreased in diabetic, compared with nondiabetic, rats and correlated with remaining relative BCA, as assessed by morphometric analysis (B and C).

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