131I-meta-iodobenzylguanidine therapy in neuroblastoma spheroids of different sizes

Abstract

Mathematical models have predicted that targeted radiotherapy of neuroblastoma with meta-iodobenzylguanidine (mIBG) is less likely to cure small rather than large micrometastases if131I is the conjugated radionuclide. This study uses multicellular tumour spheroids as an in vitro model to test the hypothesis that smaller tumours of sub-millimetre dimensions are relatively resistant to131I-mIBG. Spheroids of the human neuroblastoma cell line SK-N-BE(2c), either 250 pm or 400 pm diameter, were incubated with131I-mIBG at concentrations of up to 6.0 MBqml-1. Using both regrowth delay and spheroid ‘cure’ as endpoints, the greater vulnerability of larger spheroids was confirmed. From this in vitro result we conclude that when used in vivo131I-mIBG may spare smaller micrometastases. Therefore, either a radionuclide such as211 At which emits a shorter path length radiation should be conjugated to mIBG, or targeted radiotherapy should be combined with a treatment such as total body irradiation, the efficacy of which is not reduced in smaller tumours. © 1992 Macmillan Press Ltd.