Uptake and release of iodine-labelled m-iodobenzylguanidine in a neuroblastoma cell culture system and its importance in neuroblastoma therapy

Abstract

A neuroblastoma cell line was established from bone marrow of a patient in stage IV of the disease and used as a model system in order to elaborate experimental data of importance in neuroblastoma therapy, such as cell-drug interactions, the mode of uptake and conditions for storage and release m-Iodo benzylguanidine (MIBG) is rapidly taken up from culture medium, giving high concentrations of cell-bound radioactivity reaching a maximum level 4 h after the addition of the compound. A removal of the radiopharmacon from the culture medium causes a dramatic loss of cell-associated radioactivity, suggesting that neuroblastoma cells are not able to retain MIBG in a drug-free environment. Replacement of labelled by unlabelled MIBG prevents a similar release and maintains high levels of cellular radioactivity. Variations of cell culture conditions only result in minor changes of uptake rates, whereas a pretreatment with drugs used in neuroblastoma chemotherapy harms the cells extensively: even after a short-term exposure the cells lose the capacity for MIGB uptake and fail to recover within a long period of incubation in growth medium. The importance of our results is discussed, leading to the following suggestions: The performance of radiotherapy with labelled MIBG is recommended prior to the chemotherapy protocols. Therapeutically effective radioactivity in tumor tissues may be maintained by the additional infusion of unlabelled MIGB.