Uptake of radioiodinated
meta-iodobenzylguanidine (
MIBG) has been demonstrated in the neural crest
tumors, including
neuroblastoma,
pheochromocytoma, and
carcinoid tumors, and is presently in use diagnostically and therapeutically in these settings. Cells comprising
medulloblastoma, the most common central nervous system
malignancy in childhood, may be derived from a common germinal neuroepithelial cell as neural crest tissue, and as a result, also may have the capacity for accumulating
MIBG. To investigate this hypothesis, we measured the in vitro binding of [131I]
MIBG to 9
medulloblastoma-derived cell lines and the SK-N-SH
neuroblastoma line known to accumulate
MIBG. Seven of the
medulloblastoma lines exhibited
MIBG binding. The cell line with the greatest uptake, D384 Med, bound 11.2 +/- 0.9% of added [131I]
MIBG activity compared with 47.1 +/- 2.3% for the SK-N-SH cell line. When 2 of the cell lines, D384 Med and D458 Med, were treated with the alpha-particle emitting analogue meta-[211At]astatobenzylguanidine ([
211At]MABG), as much as a 3-log cell kill was observed in limiting dilution clonogenic assays. Exposure to considerably higher activity levels of [211At]astatide was required to achieve a similar degree of cell kill, suggesting that this cytotoxicity was not related to nonspecific effects of alpha-particle irradiation. We conclude that the uptake capacity of
medulloblastoma cell lines for [131I]
MIBG uptake in vitro, while lower than that seen in SK-N-SH
neuroblastoma cells, is sufficient to permit [
211At]MABG to be used with significant therapeutic effectiveness.