Uptake of mIBG and catecholamines in noradrenaline- and organic cation transporter-expressing cells: potential use of corticosterone for a preferred uptake in neuroblastoma- and pheochromocytoma cells |
| |
Authors: | Melanie Bayer Zyrafete Kuçi Edgar Schömig Dirk Gründemann Helmut Dittmann Rupert Handgretinger Gernot Bruchelt |
| |
Affiliation: | 1. Department of Hematology and Oncology, Children''s University Hospital, D-72072 Tuebingen, Germany;2. Department of Nuclear Medicine, University of Tuebingen, D-72072 Tuebingen, Germany;3. Department of Pharmacology, University of Koeln, D-50924 Koeln, Germany |
| |
Abstract: | For imaging of neuroblastoma and phaeochromocytoma, [123I]meta-iodobenzylguanidine ([123I]mIBG) is routinely used, whereas [18F]6-fluorodopamine ([18F]6-FDA) is sporadically applied for positron emission tomography in pheochromocytoma. Both substances are taken up by catecholamine transporters (CATs). In competition, some other cell types are able to take up catecholamines and related compounds probably by organic cation (OCT) [extraneuronal monoamine (EMT)] transporters (OCT1, OCT2, OCT3=EMT). In this study, we investigated the uptake of radioiodine-labeled meta-iodobenzylguanidine (mIBG) as well as [3H]dopamine (mimicring 6-fluorodopamine) and [3H]noradrenaline. SK-N-SH (neuroblastoma) and PC-12 (phaeochromocytoma) cells were used and compared with HEK-293 cells transfected with OCT1, OCT2 and OCT3, respectively. In order to gain a more selective uptake in CAT expressing tumor cells, different specific inhibitors were measured. Uptake of mIBG into OCT-expressing cells was similar or even better as into both CAT-expressing cell lines, whereas dopamine and noradrenaline uptake was much lower in OCT-expressing cells. In presence of corticosterone (f.c. 10?4 M], catecholamine and mIBG uptake into SK-N-SH and PC-12 cells was only slightly reduced. In contrast, this process was significantly inhibited in OCT2 and OCT3 transfected HEK-293 as well as in Caki-1 cells, which naturally express OCT3. We conclude that the well-known corticosteroid corticosterone might be used in combination with [18F]6-FDA or [123I]mIBG to improve specific imaging of neuroblastoma and pheochromocytoma and to reduce irradiation dose to nontarget organs in [131I]mIBG treatment. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|