Evaluation of Cardiac Mitochondrial Function by a Nuclear Imaging Technique using Technetium-99m-MIBI Uptake Kinetics

Document Type : Review article


Department of Nuclear Medicine, Kanazawa University, Kanazawa, Japan


Mitochondria play an important role in energy production for the cell. The proper function of a myocardial cell largely depends on the functional capacity of the mitochondria.  Therefore it is necessary to establish a novel and reliable method for a non-invasive assessment of mitochondrial function and metabolism in humans. Although originally designed for evaluating myocardial perfusion, 99mTc-MIBI can be also used to evaluate cardiac mitochondrial function. In a clinical study on ischemic heart disease, reverse redistribution of 99mTc-MIBI was evident after direct percutaneous transluminal coronary angioplasty. The presence of increased washout of 99mTc-MIBI was associated with the infarct-related artery and preserved left ventricular function. In non-ischemic cardiomyopathy, an increased washout rate of 99mTc-MIBI, which correlated inversely with left ventricular ejection fraction, was observed in patients with congestive heart failure. Increased 99mTc-MIBI washout was also observed in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and in doxorubicin-induced cardiomyopathy. Noninvasive assessment of cardiac mitochondrial function could be greatly beneficial in monitoring possible cardiotoxic drug use and in the evaluation of cardiac damage in clinical medicine.


  1. Ong SB, Hausenloy DJ. Mitochondrial morphology and cardiovascular disease. Cardiovasc Res. 2010 ;88(1):16-29.
  2. Finck BN, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease.  Circulation. 2007;115(19):2540-8.
  3. Backus M, Piwnica-Worms D, Hockett D, Kronauge J, Lieberman M, Ingram P, LeFurgey A. Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential. Am J Physiol. 1993;265(1 Pt 1):C178-87.
  4. Piwnica-Worms D, Kronauge JF, Chiu ML. Enhancement by tetraphenylborate of technetium-99m-MIBI uptake kinetics and accumulation in cultured chick myocardial cells. J Nucl Med. 1991;32(10):1992-9.
  5. Kostakoglu L, Kiratli P, Ruacan S, Hayran M, Emri S, Ergün EL, Bekdik CF. Association of tumor washout rates and accumulation of technetium-99m-MIBI with expression of P-glycoprotein in lung cancer. J Nucl Med. 1998;39(2):228-34.
  6. Maublant JC, Gachon P, Moins N. Hexakis (2-methoxy isobutylisonitrile) technetium-99m and thallium-201 chloride: uptake and release in cultured myocardial cells. J Nucl Med. 1988, 29(1):48-54.
  7. Carvalho PA, Chiu ML, Kronauge JF, Kawamura M, Jones AG, Holman BL, Piwnica-Worms D. Subcellular distribution and analysis of technetium-99m-MIBI in isolated perfused rat hearts. J Nucl Med. 1992;33(8):1516-22.
  8. Arbab AS, Koizumi K, Toyama K, Arai T, Araki T. Technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 uptake in rat myocardial cells. J Nucl Med. 1998;39(2):266-71.
  9. Piwnica-Worms D, Chiu ML, Kronauge JF. Divergent kinetics of 201Tl and 99mTc-SESTAMIBI in cultured chick ventricular myocytes during ATP depletion. Circulation. 1992;85(4):1531-41.
  10. Li QS, Frank TL, Franceschi D, Wagner HN Jr, Becher LC. Technetium-99m methoxyisobutyl isonitrile (rp30) for quantification of myocardial ischemia and reperfusion in dogs. J Nucl Med 1988;29:1539-48.
  11. Liu Z, Okada DR, Johnson G, Hocherman SD, Beju D, Okada RD. 99mTc-sestamibi kinetics predict myocardial viability in a perfused rat heart model. Eur J Nucl Med Mol Imaging 2008;35:570-8.
  12. Matsuo S, Nakae I, Tsutamoto T, Okamoto , Horie M. A novel clinical indicator using Tc-99m sestamibi for evaluating cardiac mitochondrial function in patients with cardiomyopathies. J Nucl Cardiol. 2007; 14:215-20.
  13. Hayashi D, Ohshima S, Isobe S, Cheng XW, Unno K, Funahashi H, Shinoda N, Okumura T, Hirashiki A, Kato K, Murohara T. Increased 99m Tc-sestamibi washout reflects impaired myocardial contractile and relaxation reserve during dobutamine stress due to mitochondrial dysfunction in dilated cardiomyopathy patients. J Am Coll Cardiol. 2013 (e-pub)
  14. Takeishi Y, Sukekawa H, Fujiwara S, Ikeno E, Sasaki Y, Tomoike H. Reverse redistribution of technetium-99m-sestamibi following direct PTCA in acute myocardial infarction. J Nucl Med. 1996; 37(8):1289-94.
  15. Fujiwara S, Takeishi Y, Atsumi H, Yamaki M, Takahashi N, Yamaoka M, Tojo T, Tomoike H. Prediction of functional recovery in acute myocardial infarction: comparison between sestamibi reverse redistribution and sestamibi/BMIPP mismatch. J Nucl Cardiol. 1998;5(2):119-27.
  16. Ono S, Takeishi Y, Yamaguchi H, Abe S, Tachibana H, Sato T, Kubota I. Enhanced regional washout of technetium-99m-sestamibi in patients with coronary spastic angina.  Ann Nucl Med. 2003;17(5):393-8.
  17. Sugiura T, Takase H, Toriyama T, Goto T, Ueda R, Dohi Y. Sugiura T, Takase H, Toriyama T, Goto T, Ueda R, Dohi Y. Usefulness of Tc-99m methoxyisobutylisonitrile scintigraphy for evaluating congestive heart failure. J Nucl Cardiol. 2006;13(1):64-8.
  18. Matsuo S, Matsumoto T, Nakae I, Koh T, Masuda D, Takada M, et al. Prognostic value of ECG-gated thallium-201 single-photon emission tomography in patients with coronary artery disease. Ann Nucl Med2004; 18(7):617-622.
  19. Matsuo S, Nakae I, Matsumoto T, Horie M. Impact of endothelial dysfunction on left ventricular remodeling after successful primary coronary angioplasty for acute myocardial infarction- Analysis by quantitative ECG-gated SPECT-. Ann Nucl Med 2006;20(1), 57-62.
  20. Matsuo S, Matsumoto T, Nakae I, Ito M, Nakamura Y, Takada M, Murata K, Horie M. Evaluation of cardiac resynchronization therapy in drug-resistant idiopathic dilated cardiomyopathy by means of Tc-99m tetrofosmin ECG-gated SPECT. Exp Clin Cardiol 2004;9(4);248-250.
  21. Matsuo S. Phase analysis using gated myocardial perfusion single-photon emission computed tomography imaging for evaluating cardiac dyssynchrony. Circ J. 2012;76(8):1832-3.
  22. Matsuo S, Nakajima K, Kinuya S, Sato Y, Matsumoto T, Horie M. Cardiac scintigraphic findings of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: a case report. Exp Clin Cardiol 2008;13 (2):93-95.
  23. Matsuo S, Taki J, Nakajima K. Evaluation of myocardial damage using Tc-99m sestamibi in patients with chemotherapy. J Cardiol Jpn Ed 2011;6, Suppl-I 442.
  24. Matsuo S, Nakajima K, Kinuya S. Clinical use of nuclear cardiology in the assessment of heart failure. World J Cardiol. 2010;2(10):344-356.