Cytotoxic and antitumor effects of the norepinephrine analogue meta-iodo-benzylguanidine (MIBG)

Summary Meta-iodo-benzylguanidine (MIBG) is an analogue of the neurotransmitter norepinephrine. In its radio-iodinated form, MIBG is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. The potential cytotoxicity of the unlabeled drug was tested. MIBG appeared cytotoxic in a large panel of histogenetically different cell lines without preference against tumor cells of neural origin. The cytotoxicity of MIBG was higher than of the related mono-amine precursor, meta-iodo-benzylamine (MIBA). Drugs that block adrenergic receptors and inhibitors of tyrosinase or tyrosine hydroxylase had no effect on the cytostatic properties of MIBG. However, its activity was potentiated by the pharmacological inhibition of catecholamine degradation and by inhibitors of intracellular storage. MIBG had antitumor effects on L1210 leukemia and N₁E115 neuroblastoma, grown as subcutaneous tumors in animals treated with MIBG in non-toxic schedules. The observations suggest that MIBG is cytotoxic in its native form and may contribute by this property to the clinical responses obtained with the radiolabeled drug at high concentrations.