Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2-methoxyisobutylisonitrile) technetium(I) in cultured mouse fibroblasts.
Hexakis(2-methoxyisobutylisonitrile) technetium(I) (Tc-MIBI) is representative of a class of 99mTc-based lipophilic cationic myocardial perfusion imaging agents. To test the hypothesis that the mechanism of cellular uptake may involve distribution across biologic membranes in response to membrane potential, Tc-MIBI net uptake and retention were determined in cultured mouse BALB/c 3T3, NIH 3T3, and v-src transformed NIH 3T3 fibroblasts as well as in cultured chick embryo heart cells. Isovolumic depolarization of plasma membrane potentials with 130 mM K 20 mM Cl buffer decreased Tc-MIBI net cell uptake in all preparations. In BALB/c 3T3 cells, depolarizing mitochondrial membrane potential with valinomycin in high K buffer or with the protonophore CCCP inhibited net uptake and retention of Tc-MIBI while hyperpolarizing mitochondrial and plasma membrane potentials with the K+/H+ exchanger nigericin increased Tc-MIBI net uptake. These results indicated that net cellular uptake and retention of Tc-MIBI in fibroblasts were determined by both mitochondrial and plasma membrane potentials; the gamma-emitting properties of Tc-MIBI may therefore raise the possibility of monitoring membrane potential in vivo.
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
M L
ML
Chiu
J F
JF
Kronauge
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D
Piwnica-Worms
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000502:physiology*; D002642:Chick Embryo; D005347:Fibroblasts / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D009570:Nitriles / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D017256:Technetium Tc 99m Sestamibi
D009570:Nitriles; D015609:Organotechnetium Compounds; D017256:Technetium Tc 99m Sestamibi