SPECIFIC UPTAKE OF M-[I-125]LODOBENZYLGUANIDINE IN THE HUMAN NEURO-BLASTOMA CELL-LINE SK-N-SH

Abstract

The uptke of m-[125I]iodobenzylguanidine (mlBG), 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 mlBG uptake into SK-N-SH cells: a nonspecific diffusion mechanism, and a specific, active uptake system. The latter was dramatically reduced at 4.degree. Compared to 37.degree., as well as in the presence of ouabaine or the absence of oxygen. A competitive inhibitoin of the transport of mlBG by norepinephrine was observed. When drug-treated SK-N-SH cells were incubated in fresh medium, 20 to 30% of meBG was still retained in the SK-N-SH cells 24 h after the end of incubation with meBG, whereas no meBG was detectable in SK-N-LO cells already after 1 h.