EFFECT OF MITOCHONDRIAL VIABILITY AND METABOLISM ON TECHNETIUM-99M-SESTAMIBI MYOCARDIAL RETENTION

This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi. Tc-99m-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial Tc-99m-sestamibi was localized within the mitochondrial fraction. Calcium was found to release Tc-99m-sestamibi from the mitochondrial fraction, with an IC50 of 2.54 +/- 0.98 mM. This effect was potentiated by NaCl, and inhibited by the mitochondrial calcium channel blocker ruthenium red. In vitro uptake of Tc-99m-sestamibi was found to increase from 10.5% +/- 3.0% to 61.2% +/- 0.2% with the addition of 10 mM succinate, indicating that respiration is involved. Since irreversible ischemia results in cellular and mitochondrial calcium ''overload'' and loss of mitochondrial metabolic function, Tc-99m-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability.