Smets L A, Bout B, Wisse J
Division of Experimental Therapy, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
Cancer Chemother Pharmacol. 1988;21(1):9-13. doi: 10.1007/BF00262730.
Meta-iodo-benzylguanidine (MIBG) is an analogue of the neurotransmitter norepinephrine. In its radioiodinated 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 anti-tumor 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.
间碘苄胍（MIBG）是神经递质去甲肾上腺素的类似物。以其放射性碘标记形式，MIBG在临床上用作肿瘤靶向放射性药物，用于诊断和治疗肾上腺素能肿瘤。对未标记药物的潜在细胞毒性进行了测试。MIBG在一大组组织学来源不同的细胞系中表现出细胞毒性，对神经源性肿瘤细胞无偏好性。MIBG的细胞毒性高于相关单胺前体间碘苄胺（MIBA）。阻断肾上腺素能受体的药物以及酪氨酸酶或酪氨酸羟化酶抑制剂对MIBG的细胞生长抑制特性没有影响。然而，儿茶酚胺降解的药理学抑制和细胞内储存抑制剂可增强其活性。MIBG对L1210白血病和N1E115神经母细胞瘤具有抗肿瘤作用，这些肿瘤在以无毒方案用MIBG治疗的动物中以皮下肿瘤形式生长。这些观察结果表明，MIBG以其天然形式具有细胞毒性，并且可能通过该特性对高浓度放射性标记药物所获得的临床反应有所贡献。
