Journal of Nuclear Cardiology

, Volume 1, Issue 4, pp 351–364 | Cite as

Myocardial uptake of thallium 201 and technetium 99m-labeled sestamibi after ischemia and reperfusion: Comparison by quantitative dual-tracer autoradiography in rabbits

  • Howard Weinstein
  • Christopher P. Reinhardt
  • John F. Wironen
  • Jeffrey A. Leppo
Original Articles



Myocardial scintigraphy with99mTc-labeled sestamibi (99mTc-sestamibi) or201Tl is used to assess regional perfusion in acute coronary syndromes associated with metabolic or functional abnormalities, such as acute coronary thrombosis with reperfusion and ischemia at rest. However, the initial uptake of these agents may be affected by a recent ischemic insult because the myocardial retention of these tracers depends on cellular metabolism.

Methods and Results

Accordingly,99mTc-sestamibi and201Tl were injected simultaneously in rabbits after transient brief (10 to 15 minutes, group I) or prolonged (45 to 60 minutes, group II) coronary occlusion. Accumulated subendocardial and subepicardial99mTc-sestamibi and corresponding201Tl activity were determined from autoradiographs of 30 µm short-axis slices comounted with serial tissue standards. Circumferential99mTc-sestamibi and201Tl activity profiles closely overlapped in both groups. The initial global and segmental myocardial activity per unit blood flow within the ischemic zone did not differ from unity for either tracer regardless of the duration of the ischemic insult. The initial myocardial uptake of both99mTc-sestamibi and201Tl after an acute ischemic insult reflected predominantly coronary blood flow, independent of myocardial viability.


Thus this study supports the use of both99mTc-sestamibi and201Tl as perfusion probes in acute coronary syndromes characterized by acute occlusion and reperfusion.

Key Words

sestamibi thallium 201 myocardial viability 


  1. 1.
    Okada RD. Kinetics of thallium-201 in reperfused canine myocardium after coronary artery occlusion. J Am Coll Cardiol 1984;3:1245–51.PubMedGoogle Scholar
  2. 2.
    Dilsizian V, Freedman NMT, Bacharach SL, Perrone-Filardi P, Bonow RO. Regional thallium uptake in irreversible defects: magnitude of change in thallium activity after reinjection distinguishes viable from nonviable myocardium. Circulation 1992;85:627–34.PubMedGoogle Scholar
  3. 3.
    Kayden DS, Sigal S, Soufer R, Mattera J, Zaret BL, Wackers FJT. Thallium-201 for assessment of myocardial viability: quantitative comparison of 24-hour redistribution imaging with imaging after reinjection at rest. J Am Coll Cardiol 1991;18:1480–6.PubMedGoogle Scholar
  4. 4.
    Cuocolo A, Pace L, Ricciardelli B, Chiarello M, Trimarco B, Salvatore M. Identification of viable myocardium in patients with chronic coronary artery disease: comparison of thallium-201 scintigraphy with reinjection and technetium-99m-methoxyisobutyl isonitrile. J Nucl Med 1992;33:505–11.PubMedGoogle Scholar
  5. 5.
    Perrone-Filardi P, Bacharach SL, Dilsizian V, Maurea S, Frank JA, Bonow RO. Regional left ventricular wall thickening: relation to regional uptake of 19-fluorodeoxyglucose and 201-Tl in patients with chronic coronary artery disease and left ventricular dysfunction. Circulation 1992;86:1125–37.PubMedGoogle Scholar
  6. 6.
    Bonow RO, Dilsizian V, Cuocolo A, Bacharach SL. Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction: comparison of thallium scintigraphy with reinjection and PET imaging with18F-fluorodeoxyglucose. Circulation 1991;83:26–37.PubMedGoogle Scholar
  7. 7.
    Freeman I, Grunwald AM, Hoory S, Bodenheimer MM. Effect of coronary occlusion and myocardial viability on myocardial activity of technetium-99m-sestamibi. J Nucl Med 1991;32:292–8.PubMedGoogle Scholar
  8. 8.
    Verani MS, Jeroudi MO, Mahmarian JJ, et al. Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile. J Am Coll Cardiol 1988;12:1573–81.PubMedGoogle Scholar
  9. 9.
    Beller GA, Glover DK, Edwards NC, Ruiz M, Simanis JP, Watson DD.99mTc-sestamibi uptake and retention during myocardial ischemia and reperfusion. Circulation 1993;87:2033–42.PubMedGoogle Scholar
  10. 10.
    Maublant JC, Moins N, Gachon P, Renoux M, Zhang Z, Veyre A. Uptake of technetium-99m-teboroxime in cultured myocardial cells: comparison with thallium-201 and technetium-99m-sestamibi. J Nucl Med 1993;34:255–9.PubMedGoogle Scholar
  11. 11.
    Piwnica-Worms D, Kronauge JF, Delmon L, Holman BL, Marsh JD, Jones AG. Effect of metabolic inhibition on technetium-99m-MIBI kinetics in cultured chick myocardial cells. J Nucl Med 1990;31:464–72.PubMedGoogle Scholar
  12. 12.
    Piwnica-Worms D, Chiu ML, Kronauge JF. Divergent kinetics of201Tl and99mTc-sestamibi in cultured chick ventricular myocytes during ATP depletion. Circulation 1992;85:1531–41.PubMedGoogle Scholar
  13. 13.
    Leppo JA, MacNeil PB, Moring AF, Apstein CS. Separate effects of ischemia, hypoxia, and contractility on thallium-201 kinetics in rabbit myocardium. J Nucl Med 1986;27:66–74.PubMedGoogle Scholar
  14. 14.
    Sinusas AJ, Watson DD, Cannon JM Jr, Beller GA. Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201. J Am Coll Cardiol 1989;14:1785–93.PubMedGoogle Scholar
  15. 15.
    Moore CA, Cannon J, Watson DD, Kaul S, Beller GA. Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction. Circulation 1990;81:1622–32.PubMedGoogle Scholar
  16. 16.
    Varetto T, Cantalupi D, Altieri A, Orlandi C. Emergency room technetium-99m sestamibi imaging to rule out acute myocardial ischemic events in patients with nondiagnostic electrocardiograms. J Am Coll Cardiol 1993;22:1804–8.PubMedGoogle Scholar
  17. 17.
    Homans DC, Sublett E, Dai X-Z, Bache RJ. Persistence of regional left ventricular dysfunction after exercise-induced myocardial ischemia. J Clin Invest 1986;77:66–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Robertson WS, Feigenbaum H, Armstrong WF, Dillon JC, O’Donnell J, McHenry PW. Exercise echocardiography: a clinically practical addition in the evaluation of coronary artery disease. J Am Coll Cardiol 1983;2:1085–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Weinstein H, Reinhardt CP, Leppo JA. Teboroxime, sestamibi and thallium-201 as markers of myocardial hypoperfusion: comparison by quantitative dual isotope autoradiography in rabbits. J Nucl Med 1993;34:1510–7.PubMedGoogle Scholar
  20. 20.
    Connelly CM, Vogel WM, Hernandez YM, Apstein CS. Movement of necrotic wavefront after coronary occlusion in rabbit. Am J Physiol 1982;243:H682–90.PubMedGoogle Scholar
  21. 21.
    Decker RS, Wildenthal K. Influence of methylprednisolone on ultrastructural and cytochemical changes during myocardial ischemia. Am J Pathol 1978;92:1–22.PubMedGoogle Scholar
  22. 22.
    Miura T, Downey JM, Ooiwa H, et al. Progression of myocardial infarction in a collateral flow deficient species. Jpn Heart J 1989;30:695–708.PubMedGoogle Scholar
  23. 23.
    Horneffer PPJ, Healy B, Gott VL, Gardner TJ. The rapid evolution of a myocardial infarction in an end-artery coronary preparation. Circulation 1987;76:V-39–42.Google Scholar
  24. 24.
    Rogers AW. The autoradiography of macroscopic specimens. In: Techniques of autoradiography. Amsterdam: Elsevier-North Holland Biomedical Press, 1979:313–34.Google Scholar
  25. 25.
    Ito T, Brill AB. Validity of tissue paste standards for quantitative whole-body autoradiography using short-lived radionuclides. Appl Radiat Isot 1990;41:661–7.CrossRefGoogle Scholar
  26. 26.
    Reinhardt CP, Weinstein H, Wironen J, Leppo JA. Effect of triphenyl tetrazolium chloride staining on the distribution of radiolabeled pharmaceuticals. J Nucl Med 1993;34:1722–7.PubMedGoogle Scholar
  27. 27.
    Murdock RH Jr, Chu A, Grubb M, Cobb FR. Effects of reestablishing blood flow on extent of myocardial infarction in conscious dogs. Am J Physiol 1985;18:H783–91.Google Scholar
  28. 28.
    Heyndrickx GR, Millard RW, McRitchie RJ, Maroko PR, Vatner SF. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest 1975;56:978–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Charlat ML, O’Neill PG, Hartley CJ, Roberts R, Bolli R. Prolonged abnormalities of left ventricular diastolic wall thinning in the “stunned” myocardium in conscious dogs: time course and relation to systolic function. J Am Coll Cardiol 1989;13:185–94.PubMedGoogle Scholar
  30. 30.
    Bolli R, Patel BS, Hartley CJ, Thornby JI, Jeroudi MO. Roberts R. Nonuniform transmural recovery of contractile function in stunned myocardium. Am J Physiol 1989;257:H375–85.PubMedGoogle Scholar
  31. 31.
    Weiner JM, Apstein CS, Arthur JH, Pirzada FA, Hood WB Jr. Persistence of myocardial injury following brief periods of coronary occlusion. Cardiovasc Res 1976;10:678–86.PubMedCrossRefGoogle Scholar
  32. 32.
    Bolli R. Mechanism of myocardial “stunning.” Circulation 1990;82:723–38.PubMedGoogle Scholar
  33. 33.
    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;29:48–54.PubMedGoogle Scholar
  34. 34.
    Meerdink DJ, Leppo JA. Comparison of hypoxia and ouabain effects on the first-pass myocardial uptake kinetics of Tc-99m hexakis 2-methoxyisobutyl isonitrile and thallium-201. J Nucl Med 1989;30:1500–6.PubMedGoogle Scholar
  35. 35.
    Piwnica-Worms D, Kronauge JF, Chiu ML. Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells: mitrochondrial and plasma membrane potential dependence. Circulation 1990;82:1826–38.PubMedGoogle Scholar
  36. 36.
    Beanlands RSB, Dawood F, Wen W-H, et al. Are the kinetics of technetium-99m methoxyisobutyl isonitrile affected by cell metabolism and viability? Circulation 1990;82:1802–14.PubMedGoogle Scholar
  37. 37.
    Li Q-S, Frank TL, Franceschi D, Wagner HN Jr, Becker LC. Technetium-99m methoxyisobutyl isonitrile (RP30) for quantification of myocardial ischemia and reperfusion in dogs. J Nucl Med 1988;29:1539–48.PubMedGoogle Scholar
  38. 38.
    Meerdink DJ, Leppo JA. Experimental studies of the physiologic properties of technetium-99m agents: myocardial transport of perfusion imaging agents. Am J Cardiol 1990;66:9E-15E.PubMedCrossRefGoogle Scholar
  39. 39.
    Maublant JC, Moins N, Gachon P. Uptake and release of two new Tc-99m labeled myocardial blood flow imaging agents in cultured cardiac cells. Eur J Nucl Med 1989;15:180–2.PubMedCrossRefGoogle Scholar
  40. 40.
    Chu A, Murdock RH Jr, Cobb FR. Relation between regional distribution of thallium-201 and myocardial blood flow in normal, acutely ischemic, and infarcted myocardium. Am J Cardiol 1982;50:1141–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Forman R, Kirk ES. Thallium-201 accumulation during reperfusion of ischemic myocardium: dependence on regional blood flow rather than viability. Am J Cardiol 1984;54:659–63.PubMedCrossRefGoogle Scholar
  42. 42.
    DiCola J, Downing SE, Donabedian RK, Zaret BL. Pathophysiological correlates of thallium-201 myocardial uptake in experimental infarction. Cardiovasc Res 1977;11:141–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Pohost GM, Okada RD, O’Keefe DD, et al. Thallium redistribution in dogs with severe coronary artery stenosis of fixed caliber. Circ Res 1981;48:439–46.PubMedGoogle Scholar
  44. 44.
    Sinusas AJ, Shi QX, Vitols PJ, et al. Impact of regional ventricular function, geometry, and dobutamine stress on quantitative99mTc-sestamibi defect size. Circulation 1993;88:2224–34.PubMedGoogle Scholar
  45. 45.
    Fishbein MC, Meerbaum S, Rit J, et al. Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. Am Heart J 1981;101:593–600.PubMedCrossRefGoogle Scholar
  46. 46.
    Lie JT, Pairolero PC, Holley KE, Titus JL. Macroscopic enzyme-mapping verification of large, homogeneous, experimental myocardial infarcts of predictable size and location in dogs. J Thorac Cardiovasc Surg 1975;69:599–605.PubMedGoogle Scholar
  47. 47.
    Vivaldi MT, Kloner RA, Schoen FJ. Triphenyltetrazolium staining of irreversible ischemic injury following coronary artery occlusion in rats. Am J Pathol 1985;121:522–30.PubMedGoogle Scholar
  48. 48.
    Marshall RC, Leidholdt EM Jr, Zhang D-Y, Barnett CA. Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile and thallium-201 extraction, washout and retention at varying coronary flow rates in rabbit heart. Circulation 1990;82:998–1007.PubMedGoogle Scholar
  49. 49.
    Leppo JA, Meerdink DJ. Comparative myocardial extraction of two technetium-labeled BATO derivatives (SQ30217, SQ32014) and thallium. J Nucl Med 1990;31:67–74.PubMedGoogle Scholar
  50. 50.
    Okada RD, Glover D, Gaffney T, Williams S. Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile. Circulation 1988;77:491–8.PubMedGoogle Scholar
  51. 51.
    Lambert R, Bisson G, Benjamin C, Phaneuf DC. Comparison between early (15 minutes) and delayed (60 minutes) myocardial99mTc-sestamibi SPECT imaging in detection of coronary artery disease [Abstract]. J Nucl Med 1992;33:855.Google Scholar
  52. 52.
    Johns HE, Cunningham JR. Diagnostic radiology. In: The physics of radiology. Springfield, Illinois: Charles C Thomas, 1983:557–669.Google Scholar

Copyright information

© American Society of Nuclear Cardiology 1994

Authors and Affiliations

  • Howard Weinstein
    • 1
  • Christopher P. Reinhardt
    • 1
  • John F. Wironen
    • 1
  • Jeffrey A. Leppo
    • 1
  1. 1.From the Myocardial Isotope Research Laboratory, Departments of Nuclear Medicine and Medicine (Division of Cardiology)University of Massachusetts Medical CenterWorcester

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