Influence of cisplatin and doxorubicin on I-125-meta-iodobenzylguanidine uptake in human neuroblastoma cell lines

The combination of I-131-meta-iodobenzylguanidine (MIBG) with chemotherapy has recently been employed in the treatment of advanced stage neuroblastoma with encouraging results. However, the mechanisms underlying the interacti on between these two different modalities of treatment have not yet been ex plored. In this study, human neuroblastoma cell lines pretreatment with cis platin and doxorubicin increased cellular I-125-MIBG accumulation in a dose -dependent manner. Cell cycle analysis showed that increased I-125-MIBG acc umulation correlated with the drug-induced G(2)/M phase block. Northern blo t analysis demonstrated an increase in gene expression of the noradrenaline transporter induced by doxorubicin, but not by cisplatin treatment. Increa sed I-125-MIBG accumulation was also observed in murine xenografts of the h uman neuroblastoma cell line SK-N-DZ or BE(2)M17 treated intraperitoneally (i.p.) with cisplatin or doxorubicin, respectively. These results suggest t hat the combination of I-131-MIBG.,and these drugs could selectively increa se radiation doses delivered to neuroblastomas. (C) 1999 Published by Elsev ier Science Ltd. All rights reserved.