Uptake of the cation hexakis(2-methoxyisobutylisonitrile)-technetium-99m by human carcinoma cell lines in vitro.
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.
Delmon-Moingeon
L I
LI
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Piwnica-Worms
D
D
Van den Abbeele
A D
AD
Holman
B L
BL
Davison
A
A
Jones
A G
AG
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*
D002412:Cations; D009570:Nitriles; D015609:Organotechnetium Compounds; D017256:Technetium Tc 99m Sestamibi