Meta-[131I]iodobenzylguanidine uptake and meta-[211At]astatobenzylguanidine treatment in human medulloblastoma cell lines.
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.
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
D K
DK
Strickland
G
G
Vaidyanathan
H S
HS
Friedman
M R
MR
Zalutsky
D019797:3-Iodobenzylguanidine; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001246:Astatine / Q000633:toxicity; D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002528:Cerebellar Neoplasms; D006146:Guanidines / Q000633:toxicity*; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000378:metabolism* / Q000493:pharmacokinetics; D007700:Kinetics; D008527:Medulloblastoma; D009447:Neuroblastoma; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006146:Guanidines; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; C078685:1-(3-astatobenzyl)guanidine; D019797:3-Iodobenzylguanidine; D001246:Astatine