In vitro therapeutic targeting of neuroblastomas using 125I‐labelled meta‐iodobenzylguanidine

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Abstract
The use of labelled radiopharmaceuticals such as metaiodobenzylguanidine (m‐IBG) enables neuroblastomas and other malignant cells from neural crests to be visualized. In vitro study of cellular incorporation into human neuroblastoma lines (SK‐N‐SH, SK‐N‐MC, LAN I) showed that only the SK‐N‐SH line retained iodine‐125 m‐IBG (125I‐m‐IBG) significantly. Fifty‐five percent of the initial activity was retained after 1 hr incubation at a concentration of 10−7 M of m‐IBG (specific activity: 1,480 MBq/mg). Beyond this value, m‐IBG uptake mechanisms were saturated. Study of release kinetics showed a rapid first phase (50% released after 4 hr) and a slower second phase (30% of the value retained at the equilibrium point was present after 48 hr), indicating the existence of a storage compartment. Autoradiography studies confirmed the intracytoplasmic localization of m‐IBG and showed that a low percentage (3 to 5%) of SK‐N‐SH cells strongly retained m‐IBG. Cytotoxicity tests showed that SK‐N‐SH cell growth was significantly reduced during the first days of culture, following 2 hr incubation with 1,500 KBq of 125I‐m‐IBG, whereas no toxic effect on SK‐N‐MC cells was found at the same activity. Moreover, the toxic effect observed in the SK‐N‐SH line was clearly related to the use of 125I‐m‐IBG since the same activity of 1,500 KBq of noncoupled 125I was without effect. For the latter line, colonyforming capacity was reduced for activities of 150 and 1,500 KBq of 125I‐m‐IBG, with respectively 32% and 38% lower survival rates. The cytotoxic effect of labelled m‐IBG was, however, limited in non‐saturating concentrations because the specific activity used was too low. Moreover, the low number of cells reconcentrating m‐IBG is indicative of the heterogeneous cellular composition of the SK‐N‐SH line.