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Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters.

Artikel i vetenskaplig tidskrift
Författare Lars Kölby
Peter Bernhardt
A-M Levin-Jakobsen
V Johanson
Bo Wängberg
Håkan Ahlman
Eva Forssell-Aronsson
Ola Nilsson
Publicerad i British journal of cancer
Volym 89
Nummer/häfte 7
Sidor 1383-8
ISSN 0007-0920
Publiceringsår 2003
Publicerad vid Institutionen för särskilda specialiteter, Avdelningen för radiofysik
Institutionen för de kirurgiska disciplinerna, Avdelningen för kirurgi
Sidor 1383-8
Språk en
Länkar dx.doi.org/10.1038/sj.bjc.6601276
Ämnesord 3-Iodobenzylguanidine, pharmacokinetics, Adrenal Gland Neoplasms, metabolism, Adrenergic Uptake Inhibitors, pharmacology, Animals, Antineoplastic Agents, pharmacokinetics, Blotting, Western, Chromogranin A, Chromogranins, metabolism, Clomipramine, pharmacology, Humans, Immunoenzyme Techniques, Iodine Radioisotopes, pharmacokinetics, Male, Membrane Glycoproteins, metabolism, Membrane Transport Proteins, Mice, Mice, Inbred BALB C, Mice, Nude, Nerve Tissue Proteins, metabolism, Neuroendocrine Tumors, metabolism, Neuropeptides, Pheochromocytoma, metabolism, Reserpine, pharmacology, Serotonin Uptake Inhibitors, pharmacology, Tumor Cells, Cultured, metabolism, Vesicular Biogenic Amine Transport Proteins
Ämneskategorier Cancer och onkologi, Kirurgi

Sammanfattning

The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of (123)I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated (123)I after i.v. injection of (123)I-MIBG. A high concentration of (123)I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n=4 and pheochromocytomas, n=4), reserpine significantly reduced the uptake of (123)I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of (123)I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of (123)I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.

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