Abstract
This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi.99mTc-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial99mTc-sestamibi was localized within the mitochondrial fraction. Calcium was found to release99mTc-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 of99mTc-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,99mTc-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability.
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References
Beanlands RSB, Dawood F, Wen W-H (1990) Are the kinetics of technetium-99m methoxyisobutyl isonitrile affected by cell metabolism and viability? Circulation 82:1802–1814
Chiu ML, Carvalho P, Kronauge JF, Holman BL, Jones AG, Piwnica-Worms D (1990) Mitoochondrial associated Tc-MIBI in perfused rat heart: pitfalls of tissue fractionation (abstract) J Nucl Med 31:832
Cuocolo A, Pace L, Ricciardelli B, Chiariello M, Trimarco B, Salvatore M (1992) Identification of viable myocardium in patients with chronic coronary artery disease: comparison of thallium201 scintigraphy with reinjection and technetium-99m-methoxyisobutyl isonitrile. J Nucl Med 33:505–511
Diwan JJ (1987) Mitochondrial transport of K+ and Mg2+. Biochim Biophys Acta 895:155–165
Drahota Z, Gazzoti P, Carafoli E, Rossi CS (1969) A comparison of the effects of different divalent cations on a number of mitochondrial reactions linked to ion translocation. Arch Biochem Biophys 130:267–273
Dunnett CW (1964) New tables for multiple comparisons with a control. Biometrics 20:482–491
Freeman I, Grunwald AM, Hoory S, Bodenheimer MM (1991) Effect of coronary occlusion and myocardial viability on myocardial activity of technetium-99m-sestamibi. J Nucl Med 32:292–2981
Gunter TE, Pfeiffer DR (1990) Mechanisms by which mitochondria transport calcium. Am J Physiol 258:C755-C786
Kawana M, Krizek H, Porter J, Lathrop KA, Charleston D, Harper PV (1970) Use of199Tl as a potassium analog in scanning. J Nucl Med 11:333
Mousa SA, Maina M, Brown BA, Williams SJ (1987a) Retention of RP-30 in the heart may be due to binding to a cytosolic protein. J Nucl Med 28:619
Mousa SA, Williams SJ, Sands H (1987b) Characterization of in vivo chemistry of cations in the heart. J Nucl Med 28:1351–1357
Mousa S, Cooney J, Williams SJ (1990) Relationship between regional myocardial blood flow and the distribution of99mTc-sestamibi in the presence of total coronary artery occlusion. Am Heart J 119:842–847
Okada RD, Glover D, Gaffney T, Williams SJ (1988) Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile. Circulation 77:491–498
Pennington RJ (1961) Biochemistry of dystrophic muscle. Mitochondrial succinate-tetrazolium reductase and adenosine triphosphatase. Biochem J 80:649–654
Piwnica-Worms D, Chiu ML, Kronauge JF (1990a) Effect of mitochondrial metabolic inhibitors and ionophores on Tc-MIBI accumulation in cultured chick myocytes (abstract). J Nucl Med 31:736
Piwnica-Worms D, Kronauge JF, Chin ML (1990b) Uptake and retention of hexakis(2-methoxyisobutylisonitrile) technetium (I) in cultured chick myocardial cells: mitochondrial and plasma membrane potential dependence. Circulation 82:1826–1838
Piwnica-Worms D, Kronauge JF, Davison A, Jones AG, Ingram P, LeFurgey A, Lieberman M (1990c) Mitochondrial localization of Tc-MIBI in cultured chick heart cells by electron probe x-ray microanalysis (EPXMA) (abstract). J Nucl Med 31:748
Rossi CS, Vasington FD, Carafoli E (1973) The effect of ruthenium red on the uptake and release of Ca2+ by mitochondria. Biochem Biophys Res Commun 50:846–852
Sinusas AJ, Watson DD, Cannon JM, Beller GA (1989) Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201. J Am Coll Cardiol 14:1785–1793
Sinusas AJ, Trautman KA, Bergin JD, Watson DD, Smith WH, Better G (1990) Quantification of area at risk during coronary occlusion and degree of myocardial salvage after reperfusion with technetiumn-99m 2-methoxyisobutyl isonitrile. Circulation 82:1424–1437
Sordahl LA (1984) Methods for preparation, purification and characterization of heart mitochondria. In: Dhalla NS (ed) Methods in studying cardiac membranes. CRC Press, Boca Raton, pp 65–74
Vainio H, Mela L, Chance B (1970) Energy dependent bivalent cation translocation in rat liver mitochondria. Eur J Biochem 12:387–391
Wackers FJT, Berman DS, Maddahi J, Watson DD, Beller GA, Strauss HW, Boucher CA, Picard M, Holman BL, Fridrich R, Inglese E, Delaloye B, Bischof-Delaloye A, Camin L, McKusick K (1989) Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging. J Nucl Med 30:301–311
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Crane, P., Laliberté, R., Heminway, S. et al. Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention. Eur J Nucl Med 20, 20–25 (1993). https://doi.org/10.1007/BF02261241
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DOI: https://doi.org/10.1007/BF02261241