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Pharmacokinetics and intracellular distribution of the tumor‐targeted radiopharmaceutical m ‐iodo‐benzylguanidine in SK‐N‐SH neuroblastoma and PC‐12 pheochromocytoma cells
Author(s) -
Smets Lou A.,
Janssen Ma,
Rutgers Marja,
Ritzen Karin,
Buitenhuis Corine
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910480421
Subject(s) - neuroblastoma , verapamil , pheochromocytoma , chemistry , intracellular , endocrinology , pharmacokinetics , nifedipine , medicine , cell culture , biology , calcium , biochemistry , genetics
Radioiodinated meta‐iodobenzylguanidine (MIBG) is increasingly used for the diagnosis and targeted radiotherapy of neuro‐adrenergic tumors. We have investigated various conditions for specific tumor loading and prolonged retention of this radiopharmaceutical in poorly differentiated SK‐N‐SH neuroblastoma and highly differentiated PC‐12 pheochromocytoma cells. At a constant value of drug concentration × incubation time, short incubations were superior to protracted incubations for maximal cell loading. This effect was most pronounced in the SH‐N‐SH neuroblastoma cells. In highly differentiated pheochromocytoma cells, the levels of MIBG storage remained high and unchanged during incubations up to 46 hr in label‐free medium, while primitive SK‐N‐SH cells lost 40–50% of accumulated drug by diffusion. In PC‐12 cells, susceptibility of stored MIBG to exocytotic release induced by acetylcholine or K + was similar to that of natural norepinephrine (NE) and prevented by the Ca ++ ‐channel blockers verapamil and nifedipine. Conversely, granule‐poor SK‐N‐SH cells were insensitive to exocytotic release of MIBG. Uptake and retention capacities were minimally impaired by an externally delivered radiation dose of 5 Gy to mimic the radiobiologicaf effect of 131 I‐MIBG in tumors. In pre‐irradiated cultures, drug uptake was even stimulated, probably due to enrichment in non‐proliferating cells. An autoradiographic comparison of the (sub)cellular distributions of 3 H‐noreplnephrine and 125 I‐MIBG showed that routine conditions of cell fixation and sample processing do not yield reliable results regarding localization of MIBG.