Optimizing MIBG therapy of neuroendocrine tumors: preclinical evidence of dose maximization and synergy

Nuclear Medicine and Biology
Rob J Mairs, M Boyd

Abstract

[(131)I]meta-Iodobenzylguanidine ([(131)I]MIBG) has been used for the therapy of tumors of neuroectodermal origin since the 1980s. Its role in the management of these malignancies remains controversial because of the large variation in response rates. Appreciation of the mode of conveyance of [(131)I]MIBG via the noradrenaline transporter into malignant cells and of factors that influence the activity of the uptake mechanism has indicated various ways in which the effectiveness of this type of targeted radiotherapy may be improved. Experimental observations indicate that radiolabeling of MIBG to high specific activity reduced the amount of cold competitor, thereby increasing tumor dose and minimizing pressor effects. We observed supra-additive tumor cell kill and inhibition of tumor growth following combined topotecan and [(131)I]MIBG treatment. The improved efficacy is related to topotecan's increased disruption of DNA repair. Radiation damage to targeted tumors may also be enhanced by the use of the alpha-particle emitter [(211)At]astatine rather than (131)I as radiolabel. Furthermore, recent experimental findings indicate that [(123)I]MIBG may have therapeutic potential over and above its utility as an imaging agent. It has ...Continue Reading

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