Specific uptake of m-[125I]iodobenzylguanidine in the human neuroblastoma cell line SK-N-SH.

Overview

The uptake of m-[125I]iodobenzylguanidine (mIBG), a compound structurally analogous to the antihypertensive drug guanethidine, was examined in various human cell lines. Of three neuroblastoma lines, SK-N-LO, IMR-32, and SK-N-SH, only the last showed specific uptake of the compound. In contrast, only a nonspecific uptake could be demonstrated for the other neuroblastoma lines, as well as for an osteogenic sarcoma line (SAOS-2) and a melanoma line (IgR 3). Based on analyses of uptake characteristics from Lineweaver-Burk plots it is evident that two different transport mechanisms are responsible for mIBG uptake into SK-N-SH cells: a nonspecific diffusion mechanism, and a specific, active uptake system. The latter was dramatically reduced at 4 degrees compared to 37 degrees, as well as in the presence of ouabain or the absence of oxygen. A competitive inhibition of the transport of mIBG by norepinephrine was observed. When drug-treated SK-N-SH cells were incubated in fresh medium, 20 to 30% of mIBG was still retained in the SK-N-SH cells 24 h after the end of incubation with mIBG, whereas no mIBG was detectable in SK-N-LO cells already after 1 h.