title: Uptake of the cation hexakis(2-methoxyisobutylisonitrile)-technetium-99m by human carcinoma cell lines in vitro.
abstract: Uptake of the cationic compound hexakis(2-methoxyisobutylisonitrile)-technetium-99m ([99mTc]MIBI) was examined in nine human tumor cell lines. The concentration of [99mTc]MIBI after a 1-h incubation with the compound varies from 5 to 28% of the activity in the external medium. In contrast, normal V79 cells (Chinese hamster lung fibroblasts) and human peripheral blood mononuclear cells exhibit a minimal uptake of less than 2% of the activity in the medium. Kinetic experiments with SW-13 cells indicate a rapid uptake over time (t1/2 of 10 min) until a steady state is approached whose concentration appears directly correlated with the extracellular concentration of [99mTc]MIBI with no evidence of saturation over the range tested (10(-12)-10(-9) M). [99mTc]MIBI is taken up by a temperature dependent process that is restricted to living cells. Microautoradiography demonstrates that [99mTc]MIBI is clustered in the cytoplasm around the nucleus. Given that depolarizing the plasma membrane potential in high K+ buffer results in lowering the uptake of [99mTc]-MIBI and that alteration of the mitochondrial membrane potential with valinomycin or nigericin induces, respectively, a significant decrease or increase of [99mTc]MIBI uptake, we propose that the plasma and mitochondrial membrane potentials play a major role in the uptake. These data suggest that the gamma emitter [99mTc]MIBI exhibits interesting tumor cell interaction characteristics with promise for in vivo tumor imaging.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: L I
authors.initials: LI
authors.lastname: Delmon-Moingeon
authors.forename: D
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: A D
authors.initials: AD
authors.lastname: Van den Abbeele
authors.forename: B L
authors.initials: BL
authors.lastname: Holman
authors.forename: A
authors.initials: A
authors.lastname: Davison
authors.forename: A G
authors.initials: AG
authors.lastname: Jones
mesh_terms: D001345:Autoradiography; D001692:Biological Transport; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials; D009570:Nitriles / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000378:metabolism*; D017256:Technetium Tc 99m Sestamibi; D014407:Tumor Cells, Cultured / Q000378:metabolism*
chemical_list: D002412:Cations; D009570:Nitriles; D015609:Organotechnetium Compounds; D017256:Technetium Tc 99m Sestamibi