Demonstration of high monoaminoxidase-A levels in neuroendocrine gastroenteropancreatic tumors in vitro and in vivo-tumor visualization using positron emission tomography with 11C-harmine.
OBJECTIVE
A majority of neuroendocrine gastroenteropancreatic (GEP) tumors can be detected by conventional radiological methods and scintigraphic techniques. Still there are problems to visualize small tumor lesions and non-functioning tumors. The aim of this study was to investigate some of the monoamine processing pathways of neuroendocrine GEP-tumors and try to find a new tracer substance for in vivo characterization and visualization by Positron Emission Tomography (PET).


METHODS
Autoradiography of tumor sections from 8 midgut carcinoids (MGC) and 8 endocrine pancreatic tumors (EPT) was performed with (11)C-labeled tracers for serotonin and dopamine transporters, serotonin HT2A-, dopamine D1- and muscarinic receptors and for monoamine oxidase A (MAO-A). The in vitro results initiated PET studies with (11)C-Harmine in 4 patients with MGC and 7 patients with EPT (one insulinoma, two glucagonomas and four non-functioning EPT).


RESULTS
The MAO-A-ligand Harmine expressed specific in vitro binding of 87 +/-21% for MGC and 125 +/- 50% for EPT, compared to reference tissue (rat brain, 100%). All other substances showed relatively low specific binding. (11)C-harmine-PET could visualize tumors in all patients. The mean standardized uptake value (SUV) for MGC was 7.5 +/- 3.9 and for EPT 12.9 +/- 2.7, whereas the SUV of normal liver, intestine and pancreas were 3.1 +/- 0.5, 3.4 +/- 1.2 and 8.9 +/- 3.0 respectively.


CONCLUSIONS
This study demonstrates in vitro and in vivo that neuroendocrine GEP-tumors are characterized by a high MAO-A-expression, thereby adding to the similarities of neuronal and neuroendocrine tissue. It also indicates a possible application for (11)C-harmine as a new PET-tracer for neuroendocrine GEP-tumors with the potential to visualize also non-functioning EPT's.
Orlefors
H
H
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden. hakan.orlefors@medsci.uu.se
Sundin
A
A
Fasth
K J
KJ
Oberg
K
K
Långström
B
B
Eriksson
B
B
Bergström
M
M
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006247:Harmine / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D008995:Monoamine Oxidase / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed / Q000379:methods
D014408:Biomarkers, Tumor; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D006247:Harmine; D008995:Monoamine Oxidase