6-fluorodopamine selectively destroys neuroblastoma cells expressing the noradrenaline transporter

Background. 6-Hydroxydopamine (6-OHDA) was used for ex vivo purging of bone marrow from neuroblastoma cells before autologous transplantation. However , this concept failed because of the rapid autoxidation of 6-OHDA, which le ads to the generation of cytotoxic reactive oxygen species (ROS), mainly in the incubation medium before 6-OHDA can be incorporated by neuroblastoma c ells. Procedure. We based our experiments on the theory that, in contrast, 6-fluorodopamine (6-FDA), which is slowly converted to 6-OHDA at neutral pH , is able to enter neuroblastoma cells via the noradrenaline transporter (N A-T). Therefore, most ROS are generated inside the target cells. Results. S mall amounts of ascorbate prevent the extracellular conversion of 6-FDA to 6-OHDA without affecting its cytotoxicity, leading to an even more selectiv e effect of 6-FDA. Conclusions. We conclude that 6-FDA is a promising subst ance for selective destruction of NA-T-positive neuroblastoma cells. (C) 20 00 Wiley-Liss, Inc.