Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters.
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.
Kölby
L
L
Department of Surgery, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. lars.kolby@surgery.gu.se
Bernhardt
P
P
Levin-Jakobsen
A-M
AM
Johanson
V
V
Wängberg
B
B
Ahlman
H
H
Forssell-Aronsson
E
E
Nilsson
O
O
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D015153:Blotting, Western; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000378:metabolism*; D009479:Neuropeptides; D010673:Pheochromocytoma / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins
D019797:3-Iodobenzylguanidine; D018759:Adrenergic Uptake Inhibitors; D000970:Antineoplastic Agents; D053379:Chromogranin A; D002864:Chromogranins; D002997:Clomipramine; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012110:Reserpine; D017367:Selective Serotonin Reuptake Inhibitors; D050492:Vesicular Biogenic Amine Transport Proteins; C489614:Sv2a protein, mouse; C076414:SV2A protein, human