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Demonstration of high monoamineoxidase-A levels in neuroendocrine gastroenteropancreatic tumors in vitro and in vivo: tumor visualization using positron emission tomography with 11C-harmine
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endocrin Oncology)
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2003 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 30, no 6, 669-679 p.Article in journal (Refereed) Published
Abstract [en]

Background and Aims: 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).

Subjects and Methods: Autoradiography of tumor sections from 8 midgut carcinoids (MGC) and 8 endocrine pancreatic tumors (EPT) was performed with C-11-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 C-11-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. C-11-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 C-11-harmine as a new PET-tracer for neuroendocrine GEP-tumors with the potential to visualize also non-functioning EPT's.

Place, publisher, year, edition, pages
2003. Vol. 30, no 6, 669-679 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-90210DOI: 10.1016/S0969-8051(03)00034-9OAI: oai:DiVA.org:uu-90210DiVA: diva2:162486
Available from: 2003-04-24 Created: 2003-04-24 Last updated: 2011-04-09Bibliographically approved
In thesis
1. Positron Emission Tomography in the Management of Neuroendocrine Tumors
Open this publication in new window or tab >>Positron Emission Tomography in the Management of Neuroendocrine Tumors
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s.

We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in >50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s.

Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p<0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection.

A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s).

Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 77 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1233
Medicine, Neuroendocrine tumor (NET), carcinoid, endocrine pancreatic tumor (EPT), Positron Emission Tomography (PET), serotonin-precursor, 5-hydroxytrytophan (5-HTP), Medicin
National Category
Dermatology and Venereal Diseases
Research subject
urn:nbn:se:uu:diva-3356 (URN)91-554-5561-1 (ISBN)
Public defence
2003-05-16, Roberg salen, Ingång 40, 4tr, Uppsala, 13:15
Available from: 2003-04-24 Created: 2003-04-24 Last updated: 2011-04-14Bibliographically approved

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