title: The effect of cisplatin pretreatment on the accumulation of MIBG by neuroblastoma cells in vitro.
abstract: [131I]meta-iodobenzylguanidine ([131I]MIBG) provides a means of selectively delivering radiation to neuroblastoma cells and is a promising addition to the range of agents used to treat neuroblastoma. As MIBG is now being incorporated into multimodal approaches to therapy, important questions arise about the appropriate scheduling and sequencing of the various agents employed. As the ability of neuroblastoma cells to actively accumulate MIBG is crucial to the success of this therapy, the effect of chemotherapeutic agents on this uptake capacity needs to be investigated. We report here our initial findings on the effect of cisplatin pretreatment on the neuroblastoma cell line SK-N-BE (2c). After treating these cells with therapeutically relevant concentrations of cisplatin (2 microM and 20 microM), a stimulation in uptake of [131I]MIBG was observed. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that this effect was due to increased expression of the noradrenaline transporter. These results suggest that appropriate scheduling of cisplatin and [131I]MIBG may lead to an increase in tumour uptake of this radiopharmaceutical with consequent increases in radiation dose to the tumour.
authors.affiliation: Department of Radiation Oncology, University of Glasgow, CRC Beatson Laboratories, Bearsden, UK.
authors.forename: A
authors.initials: A
authors.lastname: Armour
authors.forename: S H
authors.initials: SH
authors.lastname: Cunningham
authors.forename: M N
authors.initials: MN
authors.lastname: Gaze
authors.forename: T E
authors.initials: TE
authors.lastname: Wheldon
authors.forename: R J
authors.initials: RJ
authors.lastname: Mairs
mesh_terms: D019797:3-Iodobenzylguanidine; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D002452:Cell Count; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D007462:Iodobenzenes / Q000493:pharmacokinetics*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027981:Symporters; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D007462:Iodobenzenes; D009363:Neoplasm Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D019797:3-Iodobenzylguanidine; D002945:Cisplatin