Preclinical Assessment of Strategies for Enhancement of Metaiodobenzylguanidine Therapy of Neuroendocrine Tumors

摘要: By virtue of its high affinity for the norepinephrine transporter (NET), [ 131 I]metaiodobenzylguanidine ([ I]MIBG) has been used therapy tumors neuroectodermal origin more than 25 years. Although not yet universally adopted, I]MIBG targeted radiotherapy remains a highly promising means management neuroblastoma, pheochromocytoma, and carcinoids. Appreciation mode conveyance into malignant cells factors that influence activity uptake mechanism indicated variety increasing effectiveness this type treatment. Studies in model systems revealed radiolabeling MIBG to specific reduced amount cold competitor, thereby tumor dose minimizing pressor effects. Increased radiotoxicity might also be achieved by use α-particle emitter 211 At]astatine rather I as radiolabel. Recently it demonstrated potent cytotoxic bystander effects were induced I]MIBG, 123 At]meta-astatobenzylguanidine. Discovery structure could increase therapeutic ratio achievable radiotherapy. combined with topotecan produced supra-additive cytotoxicity vitro growth delay vivo. The enhanced antitumor effect was consistent failure repair DNA damage. Initial findings suggest further enhancement efficacy triple combination drugs disrupt alternative tumor-specific pathways synergize only abut topotecan. With these ploys, is expected advances will made toward optimization tumors.