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Effect of Mitochondrial and Plasma Membrane Potentials on Accumulation of Hexakis (2-Methoxyisobutylisonitrile)Technetium(I) in Cultured Mouse Fibroblasts

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachussetts

Correspondence: For reprints contact: David Piwnica-Worms, MD, PhD, Department of Radiology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.

ABSTRACT

Hexakis(2-methoxyisobutylisonitrile)technetium(I) (Tc-MIBI) is representative of a class of ^99mTc-based lipophilic cationic mycocardial 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 Ci 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.

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