Key result
99Tc-MIBI concentrates ~1,000 times into mitochondria, enabling calculation of inner membrane potential.
Why the study?
Tc-MIBI is used clinically to evaluate myocardial perfusion, but direct assessment of its subcellular distribution in heart tissue was needed to understand its mitochondrial sequestration.
99Tc-MIBI concentrates in mitochondria in a dose-dependent manner, allowing for in situ investigation of cellular bioenergetics and calculation of mitochondrial membrane potential.
Enables mitochondrial potential assessment in animal models; leaves open translation to human bioenergetics research.
Hexakis (2-methoxyisobutylisonitrile) technetium-99m (99mTc-MIBI) is a gamma-emitting radiopharmaceutical probe currently in clinical use to evaluate myocardial perfusion. Biochemical and cellular pharmacological studies have suggested that Tc-MIBI, a lipophilic cation, is sequestered in mitochondria in response to transmembrane potentials. To assess directly the subcellular distribution of the probe in heart tissue, cultured chick heart cells were analyzed by electron-probe X-ray microanalysis (EPXMA) following equilibration in micromolar concentrations of carrier-added 99Tc-MIBI, the ground-state radiopharmaceutical. Quantitation of the physiological elements Na, Ca, Mg, K, S, P, and Cl was correlated with exposure to increasing concentrations of 99Tc-MIBI. EPXMA signals indicated that 99Tc-MIBI was concentrated up to 1,000 times into mitochondria in a dose-dependent fashion based on measured Tc content in the mitochondria. Inner membrane potential (delta psi) of individual mitochondria was calculated as -117 mV using the Nernst equation. Concentrations of 99Tc-MIBI > 36 microM caused a significant efflux of K and Mg from the cell, as well as an increase in Cl in the mitochondria. Comparison of cell ultrastructure with conventional electron microscopy at extracellular 99Tc-MIBI concentrations of 36-72 microM showed no changes compared with control. 99Tc-MIBI allows valuable in situ investigation of cellular bioenergetics with EPXMA by quantitation of delta psi.
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Backus et al. (1993) studied this question. 99Tc-MIBI vs. control was evaluated on subcellular distribution and mitochondrial membrane potential. 99Tc-MIBI was concentrated up to 1,000 times into mitochondria in a dose-dependent fashion, allowing calculation of an inner membrane potential of -117 mV.
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