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 con centrated by various tumours of neuroectodermal origin. Radio-iodinate d [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-s ensitive uptake of [I-131]MIBG was much slower than of [H-3]serotonin, but after prolonged incubation high and serotonin-equivalent uptake l evels 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 neu roadrenergic Uptake-I in SK-N-SH neuroblastoma and PCl2 pheochromocyto ma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PCl2 cells, similarly to that of serotonin in platelets. However, t he drug was 100-fold more effective in inhibiting platelet transport o f MIBG than of serotonin. The results indicate that MIBG uptake in pla telets is not mediated by a neuro-adrenergic Uptake-1, but probably pr oceeds via the serotonin transport system. MIBG concentration by plate lets 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 selective ly blocked by fluvoxamine in concentrations which minimally affected i ts accumulation in neuro-adrenergic target cells.