Neuroblastoma cells expressing the noradrenaline transporter are destroyedmore selectively by 6-fluorodopamine than by 6-hydroxydopamine

6-Hydroxydopamine (6-OHDA) has been used for lesioning catecholaminergic ne urons and attempted purging of neuroblastoma cells from hematopoietic stem cells in autologous bone marrow transplantation (ABMT). Neurotoxicity is me diated primarily by reactive oxygen species. In ABMT, 6-OHDA, as a purging agent, has been unsuccessful. At physiological pH it autooxidizes before ta rgeted uptake, resulting in nonspecific cytotoxicity of nontarget cells. A catecholamine analogue, similar to 6-OHDA but with a lower rate of autooxid ation enabling uptake by target cells, is thus required. Electron paramagne tic resonance spectra in this study show that 6-fluorodopamine (6-FDA) hydr olyzes slowly to 6-OHDA at physiological pH. Oxygen consumption, H2O2, and quinone production are found to be intermediate between those of 6-OHDA and dopamine (DA), Relative neurotoxicity of these compounds was assessed by c ell viability and DNA damage in the human neuroblastoma lines SH-SY5Y and S K-N-LO, which express and lack the noradrenaline transporter, respectively, Specific uptake of DA and 6-FDA by SH-SY5Y cells was demonstrated by compe titive m-[I-131]iodobenzylguanidine uptake inhibition. The competition by 6 -OHDA was low owing to rapid autooxidation during incubation with equal tox icity toward both cell types. 6-FDA toxicity was preferential for SH-SY5Y c ells and reduced in the presence of desipramine, a catecholamine uptake inh ibitor. We demonstrate that 6-FDA cytotoxicity is more specific for cells e xpressing catecholamine reuptake systems than is 6-OHDA cytotoxicity.