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

Abstract

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 123I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOTI, all organs and xenografted tumours accumulated 123I after i.v. injection of 123I-MiBG. A high concentration of 123I was maintained in GOTI tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOTI and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n = 4 and pheochromocytomas, n = 4), reserpine significantly reduced the uptake of 123I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of 123I-MIBG in GOTI 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 123I-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. © 2003 Cancer Research UK.