MEMBRANE-POTENTIAL DETERMINATION IN LARGE UNILAMELLAR VESICLES WITH HEXAKIS(2-METHOXYISOBUTYLISONITRILE) TECHNETIUM(I)

The accumulation of the lipophilic cation hexakis (2-methoxyisobutylisonitrile)technetium (Tc-99m-MIBI) within large unilamellar vesicles made from egg phosphatidylcholine was examined as a function of time and membrane potential (E(m)). Equilibrium distribution occurred within minutes at 30-degrees-C. The transmembrane distribution of Tc-MIBI was measured at E(m) = 0 mV and at a series of negative membrane potentials. The distribution of Tc-MIBI was in close agreement with the Nernst equation for passive distribution of a permeant ion across a bilayer, permitting the membrane potential to be predicted from Tc-MIBI distribution. In this respect, Tc-MIBI behaves similarly to other radioprobes of membrane potential, but with unique properties including high specific activity (10(9) Ci/mol), rapid kinetics of distribution, low potential-independent binding, and short half-life (6.02 h). The results indicate a mechanism for tissue accumulation of Tc-MIBI in vivo that may in part account for its utility in clinical imaging of ischemic myocardium.