Neuroblastoma is a pediatric malignancy with a poor prognosis at least partly attributable to an early pattern of dissemination. New approaches to treatment of micrometastases include targeted radiotherapy using radiolabeled antibodies or molecules which are taken up preferentially by tumor cells. Multicellular tumor spheroids (MTS) resemble micrometastases during the avascular phase of their development. A human neuroblastoma cell line (NBl-G) was grown as MTS and incubated briefly with a radiolabeled monoclonal antibody (131I-UJ13A) directed against neuroectodermal antigens. Spheroid response was evaluated in terms of regrowth delay or proportion sterilized. A dose-response relationship was demonstrated in terms of 131I activity or duration of incubation. Control experiments using unlabeled UJ13A, radiolabeled nonspecific antibody (T2.10), radiolabeled human serum albumin, and radiolabeled sodium iodide showed these to be relatively ineffective compared to 131I-UJ13A. The cell line NBl-G grown as MTS has also been found to preferentially accumulate the radiolabeled catecholamine precursor molecule m-[131I]iodobenzylguanidine compared to cell lines derived from other tumor types. NBl-G cells grown as MTS provide a promising laboratory model for targeted radiotherapy of neuroblastoma micrometastases using radiolabeled antibodies or m-iodobenzylguanidine.

译文

:神经母细胞瘤是一种儿童恶性肿瘤,预后较差,至少部分归因于早期传播。治疗微转移的新方法包括使用放射标记抗体或分子优先被肿瘤细胞吸收的分子进行靶向放射治疗。多细胞肿瘤球(MTS)在其发展的无血管阶段类似于微转移。将人神经母细胞瘤细胞系(NB1-G)生长为MTS,并与针对神经外胚层抗原的放射性标记单克隆抗体(131I-UJ13A)短暂孵育。根据再生延迟或灭菌比例评估球体反应。通过131I活性或孵育持续时间证明了剂量-反应关系。使用未标记的UJ13A,放射性标记的非特异性抗体(T2.10),放射性标记的人血清白蛋白和放射性标记的碘化钠进行的对照实验显示,与131I-UJ13A相比,它们相对无效。与衍生自其他肿瘤类型的细胞系相比,还发现以MTS形式生长的细胞系NB1-G优先积累放射性标记的儿茶酚胺前体分子m- [131I]碘代苄基胍。生长为MTS的NB1-G细胞为使用放射标记抗体或间碘苄基胍的神经母细胞瘤微转移靶向放疗提供了有希望的实验室模型。

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