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Basic properties of myocardial perfusion agents

Thomas A Holly, MD
Preeti Kansal, MD
Section Editor
Warren J Manning, MD
Deputy Editor
Brian C Downey, MD, FACC


Radionuclide myocardial perfusion imaging (MPI) involves the visualization of a radiopharmaceutical that is distributed throughout the myocardium in proportion to coronary blood flow, thereby permitting the determination of relative blood flow in various regions of the heart. Regional coronary blood flow (delivery) determines the amount of tracer activity within a specific area; close correlation between flow and activity has been demonstrated with the currently available radiopharmaceuticals over a physiologic range of coronary blood flow.

Perfusion imaging is dependent upon the physical properties of the radiolabeled tracer, its delivery, and its extraction and retention by the myocyte. Both cell membrane integrity and energy utilization are necessary for intracellular extraction and retention of tracer. Thus, retained tracer activity is synonymous with myocyte viability. Revascularization of such segments can lead to improvement in left ventricular function. (See "Evaluation of hibernating myocardium" and "Ischemic cardiomyopathy: Treatment and prognosis".)

The ideal perfusion agent would have the following characteristics:

High first pass myocardial extraction

Linear relationship between uptake and flow

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Literature review current through: Sep 2017. | This topic last updated: Jan 07, 2016.
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  1. Lebowitz E, Greene MW, Fairchild R, et al. Thallium-201 for medical use. I. J Nucl Med 1975; 16:151.
  2. 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.
  3. Meerdink DJ, Leppo JA. Comparison of hypoxia and ouabain effects on the myocardial uptake kinetics of technetium-99m hexakis 2-methoxyisobutyl isonitrile and thallium-201. J Nucl Med 1989; 30:1500.
  4. Strauss HW, Harrison K, Langan JK, et al. Thallium-201 for myocardial imaging. Relation of thallium-201 to regional myocardial perfusion. Circulation 1975; 51:641.
  5. Nielsen AP, Morris KG, Murdock R, et al. Linear relationship between the distribution of thallium-201 and blood flow in ischemic and nonischemic myocardium during exercise. Circulation 1980; 61:797.
  6. Mays AE Jr, Cobb FR. Relationship between regional myocardial blood flow and thallium-201 distribution in the presence of coronary artery stenosis and dipyridamole-induced vasodilation. J Clin Invest 1984; 73:1359.
  7. Pohost GM, Zir LM, Moore RH, et al. Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-201. Circulation 1977; 55:294.
  8. Beller GA, Watson DD, Ackell P, Pohost GM. Time course of thallium-201 redistribution after transient myocardial ischemia. Circulation 1980; 61:791.
  9. Medrano, R, Mahmarian, et al. Nitroglycerine before injection of thallium-201 enhances detection of reversible hypoperfusion via collateral blood flow: A randomized, double blind parallel, placebo-controlled trial using quantitative tomography (abstract). J Am Coll Cardiol 1993; 21:221A.
  10. Perlmutter NS, Wilson RA, Angello DA, et al. Ribose facilitates thallium-201 redistribution in patients with coronary artery disease. J Nucl Med 1991; 32:193.
  11. Weiss AT, Maddahi J, Lew AS, et al. Reverse redistribution of thallium-201: a sign of nontransmural myocardial infarction with patency of the infarct-related coronary artery. J Am Coll Cardiol 1986; 7:61.
  12. Soufer R, Dey HM, Lawson AJ, et al. Relationship between reverse redistribution on planar thallium scintigraphy and regional myocardial viability: a correlative PET study. J Nucl Med 1995; 36:180.
  13. Wackers FJ, Berman DS, Maddahi J, et al. Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging. J Nucl Med 1989; 30:301.
  14. Piwnica-Worms D, Kronauge JF, Chiu ML. Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells. Mitochondrial and plasma membrane potential dependence. Circulation 1990; 82:1826.
  15. Maublant JC, Moins N, Gachon P, et al. Uptake of technetium-99m-teboroxime in cultured myocardial cells: comparison with thallium-201 and technetium-99m-sestamibi. J Nucl Med 1993; 34:255.
  16. Leppo JA, Meerdink DJ. Comparison of the myocardial uptake of a technetium-labeled isonitrile analogue and thallium. Circ Res 1989; 65:632.
  17. Glover DK, Okada RD. Myocardial kinetics of Tc-MIBI in canine myocardium after dipyridamole. Circulation 1990; 81:628.
  18. Okada RD, Glover D, Gaffney T, Williams S. Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile. Circulation 1988; 77:491.
  19. Sinusas AJ, Trautman KA, Bergin JD, et al. Quantification of area at risk during coronary occlusion and degree of myocardial salvage after reperfusion with technetium-99m methoxyisobutyl isonitrile. Circulation 1990; 82:1424.
  20. DePuey EG, Rozanski A. Using gated technetium-99m-sestamibi SPECT to characterize fixed myocardial defects as infarct or artifact. J Nucl Med 1995; 36:952.
  21. Udelson JE, Coleman PS, Metherall J, et al. Predicting recovery of severe regional ventricular dysfunction. Comparison of resting scintigraphy with 201Tl and 99mTc-sestamibi. Circulation 1994; 89:2552.
  22. Maurea S, Cuocolo A, Soricelli A, et al. Enhanced detection of viable myocardium by technetium-99m-MIBI imaging after nitrate administration in chronic coronary artery disease. J Nucl Med 1995; 36:1945.
  23. Bisi G, Sciagrà R, Santoro GM, et al. Technetium-99m-sestamibi imaging with nitrate infusion to detect viable hibernating myocardium and predict postrevascularization recovery. J Nucl Med 1995; 36:1994.
  24. Sciagrà R, Bisi G, Santoro GM, et al. Comparison of baseline-nitrate technetium-99m sestamibi with rest-redistribution thallium-201 tomography in detecting viable hibernating myocardium and predicting postrevascularization recovery. J Am Coll Cardiol 1997; 30:384.
  25. Higley B, Smith FW, Smith T, et al. Technetium-99m-1,2-bis[bis(2-ethoxyethyl) phosphino]ethane: human biodistribution, dosimetry and safety of a new myocardial perfusion imaging agent. J Nucl Med 1993; 34:30.
  26. Jain D, Wackers FJ, Mattera J, et al. Biokinetics of technetium-99m-tetrofosmin: myocardial perfusion imaging agent: implications for a one-day imaging protocol. J Nucl Med 1993; 34:1254.
  27. Platts EA, North TL, Pickett RD, Kelly JD. Mechanism of uptake of technetium-tetrofosmin. I: Uptake into isolated adult rat ventricular myocytes and subcellular localization. J Nucl Cardiol 1995; 2:317.
  28. Sinusas AJ, Shi Q, Saltzberg MT, et al. Technetium-99m-tetrofosmin to assess myocardial blood flow: experimental validation in an intact canine model of ischemia. J Nucl Med 1994; 35:664.
  29. Zaret BL, Rigo P, Wackers FJ, et al. Myocardial perfusion imaging with 99mTc tetrofosmin. Comparison to 201Tl imaging and coronary angiography in a phase III multicenter trial. Tetrofosmin International Trial Study Group. Circulation 1995; 91:313.
  30. Borges-Neto S, Tuttle RH, Shaw LK, et al. Outcome prediction in patients at high risk for coronary artery disease: comparison between 99mTc tetrofosmin and 99mTc sestamibi. Radiology 2004; 232:58.
  31. Flamen P, Bossuyt A, Franken PR. Technetium-99m-tetrofosmin in dipyridamole-stress myocardial SPECT imaging: intraindividual comparison with technetium-99m-sestamibi. J Nucl Med 1995; 36:2009.
  32. Shaw LJ, Hendel R, Borges-Neto S, et al. Prognostic value of normal exercise and adenosine (99m)Tc-tetrofosmin SPECT imaging: results from the multicenter registry of 4,728 patients. J Nucl Med 2003; 44:134.
  33. Galassi AR, Azzarelli S, Tomaselli A, et al. Incremental prognostic value of technetium-99m-tetrofosmin exercise myocardial perfusion imaging for predicting outcomes in patients with suspected or known coronary artery disease. Am J Cardiol 2001; 88:101.
  34. Shanoudy H, Raggi P, Beller GA, et al. Comparison of technetium-99m tetrofosmin and thallium-201 single-photon emission computed tomographic imaging for detection of myocardial perfusion defects in patients with coronary artery disease. J Am Coll Cardiol 1998; 31:331.
  35. Soman P, Taillefer R, DePuey EG, et al. Enhanced detection of reversible perfusion defects by Tc-99m sestamibi compared to Tc-99m tetrofosmin during vasodilator stress SPECT imaging in mild-to-moderate coronary artery disease. J Am Coll Cardiol 2001; 37:458.
  36. Koplan BA, Beller GA, Ruiz M, et al. Comparison between thallium-201 and technetium-99m-tetrofosmin uptake with sustained low flow and profound systolic dysfunction. J Nucl Med 1996; 37:1398.
  37. Galassi AR, Tamburino C, Grassi R, et al. Comparison of technetium 99m-tetrofosmin and thallium-201 single photon emission computed tomographic imaging for the assessment of viable myocardium in patients with left ventricular dysfunction. J Nucl Cardiol 1998; 5:56.
  38. Acampa W, Cuocolo A, Petretta M, et al. Tetrofosmin imaging in the detection of myocardial viability in patients with previous myocardial infarction: comparison with sestamibi and Tl-201 scintigraphy. J Nucl Cardiol 2002; 9:33.
  39. Takahashi N, Tamaki N, Tadamura E, et al. Combined assessment of regional perfusion and wall motion in patients with coronary artery disease with technetium 99m tetrofosmin. J Nucl Cardiol 1994; 1:29.
  40. Heller, GV, Stowers, et al. Acute emergency department Tc-99m tetrofosmin SPECT imaging in patients with chest pain and nondiagnostic ECG: Results of a multicenter trial (abstract). Circulation 1996; 94:I.
  41. Machac J. Cardiac positron emission tomography imaging. Semin Nucl Med 2005; 35:17.
  42. Heller GV, Calnon D, Dorbala S. Recent advances in cardiac PET and PET/CT myocardial perfusion imaging. J Nucl Cardiol 2009; 16:962.
  43. Jaarsma C, Leiner T, Bekkers SC, et al. Diagnostic performance of noninvasive myocardial perfusion imaging using single-photon emission computed tomography, cardiac magnetic resonance, and positron emission tomography imaging for the detection of obstructive coronary artery disease: a meta-analysis. J Am Coll Cardiol 2012; 59:1719.
  44. Mc Ardle BA, Dowsley TF, deKemp RA, et al. Does rubidium-82 PET have superior accuracy to SPECT perfusion imaging for the diagnosis of obstructive coronary disease?: A systematic review and meta-analysis. J Am Coll Cardiol 2012; 60:1828.
  45. Parker MW, Iskandar A, Limone B, et al. Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis. Circ Cardiovasc Imaging 2012; 5:700.
  46. Anagnostopoulos C, Almonacid A, El Fakhri G, et al. Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity. Eur J Nucl Med Mol Imaging 2008; 35:1593.
  47. Ziadi MC, Beanlands RS. The clinical utility of assessing myocardial blood flow using positron emission tomography. J Nucl Cardiol 2010; 17:571.
  48. Lortie M, Beanlands RS, Yoshinaga K, et al. Quantification of myocardial blood flow with 82Rb dynamic PET imaging. Eur J Nucl Med Mol Imaging 2007; 34:1765.
  49. Lautamäki R, George RT, Kitagawa K, et al. Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis. Eur J Nucl Med Mol Imaging 2009; 36:576.
  50. Schlyer DJ. PET tracers and radiochemistry. Ann Acad Med Singapore 2004; 33:146.
  51. Tillisch J, Brunken R, Marshall R, et al. Reversibility of cardiac wall-motion abnormalities predicted by positron tomography. N Engl J Med 1986; 314:884.
  52. vom Dahl J, Altehoefer C, Sheehan FH, et al. Effect of myocardial viability assessed by technetium-99m-sestamibi SPECT and fluorine-18-FDG PET on clinical outcome in coronary artery disease. J Nucl Med 1997; 38:742.
  53. Allman KC, Shaw LJ, Hachamovitch R, Udelson JE. Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis. J Am Coll Cardiol 2002; 39:1151.
  54. Henze E, Schelbert HR, Barrio JR, et al. Evaluation of myocardial metabolism, with N-13- and C-11-labeled amino acids and positron computed tomography. J Nucl Med 1982; 23:671.
  55. El Fakhri G, Kardan A, Sitek A, et al. Reproducibility and accuracy of quantitative myocardial blood flow assessment with (82)Rb PET: comparison with (13)N-ammonia PET. J Nucl Med 2009; 50:1062.
  56. Herzog BA, Husmann L, Valenta I, et al. Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography added value of coronary flow reserve. J Am Coll Cardiol 2009; 54:150.
  57. Kapur A, Latus KA, Davies G, et al. A comparison of three radionuclide myocardial perfusion tracers in clinical practice: the ROBUST study. Eur J Nucl Med Mol Imaging 2002; 29:1608.