UPTAKE OF THE NEURON-BLOCKING AGENT METAIODOBENZYLGUANIDINE AND SEROTONIN BY HUMAN PLATELETS AND NEURO-ADRENERGIC TUMOR-CELLS

The adrenomedulla-imaging agent meta-iodobenzylguanidine (MIBG) is concentrated by various tumours of neuroectodermal origin. Radio-iodinated [I-131]MIBG is therefore increasingly used for diagnosis and therapy of these disorders. To study the cause of thrombocytopenia associated with [I-131]MIBG therapy, we investigated the uptake of MIBG in human platelets in comparison with that of serotonin. Specific imipramine-sensitive uptake of [I-131]MIBG was much slower than of [H-3]serotonin, but after prolonged incubation high and serotonin-equivalent uptake levels were observed. Accumulation of MIBG saturated at 10- to 100-fold higher concentration than serotonin, and the affinity for uptake and intracellular storage in platelets was much higher for serotonin than for MIBG. Conversely, serotonin was not detectably concentrated by neuroadrenergic Uptake-I in SK-N-SH neuroblastoma and PCl2 pheochromocytoma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PCl2 cells, similarly to that of serotonin in platelets. However, the drug was 100-fold more effective in inhibiting platelet transport of MIBG than of serotonin. The results indicate that MIBG uptake in platelets is not mediated by a neuro-adrenergic Uptake-1, but probably proceeds via the serotonin transport system. MIBG concentration by platelets was at least as efficient as in neuro-adrenergic tumour cells and has therefore (radio)biological potential for injuring these cells or precursor megakaryocytes. Platelet up-take of MIBG could be selectively blocked by fluvoxamine in concentrations which minimally affected its accumulation in neuro-adrenergic target cells.