In vitro pharmacology of metaiodobenzylguanidine uptake, storage and release in human neuroblastoma cells.
Four human neuroblastoma (NB) cell lines (LAN-5, SK-N-BE(2)C, GI-LI-N, and GI-CA-N) have been investigated for their ability to take up and store [125I]metaiodobenzylguanidine (125I-MIBG) in vitro. Only SK-N-BE(2)C and LAN-5 cells were able to specifically take up MIBG, with the former cell line showing a more efficient retention of the radiotracer. 125I-MIBG incorporation in both cell lines was inhibited by norepinephrine, desipramine, ouabain and energy depletion. Thus, all the major criteria for specific (type 1) uptake were fulfilled. Conversely, GI-LI-N and GI-CA-N cells did not show any specific uptake. Pharmacological manipulations aimed at defining the intracellular site(s) of 125I-MIBG storage clearly showed that the radiotracer is not accumulated in the reserpine-sensitive neurosecretory granules and vesicles in NB cells, contrary to what has been observed in a chromaffin derived tumor cell line (PC12). Our study provides new and suitable models to investigate in vitro the molecular and cellular pharmacology of MIBG in NB cells.
Montaldo
P G
PG
Pediatric Oncology Research Laboratory, G. Gaslini Children's Hospital, Genoa, Italy.
Carbone
R
R
Lanciotti
M
M
Ponzoni
M
M
Cornaglia-Ferraris
P
P
D019797:3-Iodobenzylguanidine; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000493:pharmacokinetics*; D009447:Neuroblastoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine