I-131 METAIODOBENZYLGUANIDINE THERAPY IN NEUROBLASTOMA SPHEROIDS OF DIFFERENT SIZES

Mathematical models have predicted that targeted radiotherapy of neuroblastoma with meta-iodobenzylguanidine (mIBG) is less likely to cure small rather than large micrometastases if I-131 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 to I-131-mIBG. Spheroids of the human neuroblastoma cell line SK-N-BE(2c), either 250 mum or 400 mum diameter, were incubated with I-131-mIBG at concentrations of up to 6.0 MBq ml-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 vivo I-131-mIBG may spare smaller micrometastases. Therefore, either a radionuclide such as At-211 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.