REVERSE TRANSCRIPTASE-POLYMERASE CHAIN-REACTION (RT-PCR) ANALYSIS OF MONOAMINE TRANSPORTERS IN NEUROBLASTOMA CELL-LINES - CORRELATIONS TO METAIODOBENZYLGUANIDINE (MIBG) UPTAKE AND TYROSINE-HYDROXYLASE GENE-EXPRESSION

Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently, it has been demonstrated that MIBG is incorporated into neu roblastoma cells by the noradrenaline transporter. In vitro experiment s on SK-N-SH human neuroblastoma cells performed in the present study showed that uptake of MIBG is inhibited by noradrenaline, more so by d opamine and to a lesser extent, by serotonin, indicating that the resp ective transporters may also contribute to MIBG uptake. However, neith er dopamine nor serotonin transporter gene expression was detected. No radrenaline transporter gene expression was found in 4 of 6 investigat ed cell lines, which correlated with specific MIBG uptake. Furthermore , an inverse correlation of noradrenaline transporter and tyrosine hyd roxylase gene expression, the key regulatory enzyme of catecholamine s ynthesis, was observed. These data show that MIBG is specifically inco rporated only in neuroblastoma cells in which there is noradrenaline t ransporter gene expression. Furthermore, the catecholamine status in n euroblastoma cells is regulated by a coordinate expression of the key elements of catecholamine synthesis and reuptake systems.