Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Heterogeneity of regional nitrogen 13-labeled ammonia tracer distribution in the normal human heart: Comparison with rubidium 82 and copper 62-labeled PTSM

  • 61 Accesses

  • 31 Citations

Abstract

Background

Recent reports on13N-labeled ammonia (13N-ammonia) positron emission tomographic (PET) imaging have suggested a relative reduction of measured tracer activity in the posterolateral wall. Such inhomogeneity of tracer distribution could potentially affect accuracy for detection of disease. The aim of this study was to compare the regional distribution of13N-ammonia with82Rb and62Cu-labeled PTSM (62Cu-PTSM) to identify tracer-specific patterns that may be important in the clinical interpretation of cardiac flow studies.

Methods and Results

Twenty-eight healthy volunteers underwent PET imaging at rest with either13N-ammonia (n=14),82Rb (n=8), or62Cu-PTSM (n=6). Eight subjects given13N-ammonia also underwent imaging after adenosine. Activity measured in the posterolateral wall on transaxial images was significantly lower than in the septum for13N-ammonia, both at rest (p<0.005) and after adenosine (p<0.05). No differences were detected for82Rb or62Cu-PTSM. The septum/posterolateral wall activity ratios for13N-ammonia,82Rb, and62Cu-PTSM were 1.15±0.07, 1.00±0.06, and 0.97±0.08, respectively (p<0.001). Regional analysis of image data showed the percent of maximal activity data for13N-ammonia in the lateral wall to be less than that of other regions (p<0.001) and in the inferior wall to be greater than in the anterior and lateral walls (p<0.001). For62Cu-PTSM, activity in the inferior wall was greater than that in other regions (p<0.005). No regional differences were detected for82Rb.

Conclusions

The relatively increased wall activity with13N-ammonia and62Cu-PTSM is most likely due to cross-contamination of activity from the liver. The significant reduction in activity in the lateral wall with13N-ammonia, which persists after adenosine, is most likely related to regional heterogeneity in13N-ammonia retention and may reflect regional differences in metabolic-trapping mechanisms for13N-ammonia. Further investigation is required to elucidate the underlying mechanism of this phenomenon. Reduced tracer retention in the lateral wall segment as a normal variant must be considered when evaluating clinical13N-ammonia PET studies.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Walsh M, Bergmann S, Steele R, et al. Delineation of impaired regional myocardial perfusion by positron emission tomography with H2-15O. Circulation 1988;78:612–20.

  2. 2.

    Bergmann S, Herrero P, Markham J, Weinheimer C, Walsh M. Noninvasive quantification of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. J Am Coll Cardiol 1989;14:639–52.

  3. 3.

    Hutchins G, Schwaiger M, Rosenspire K, Krivokapich J, Schelbert H, Kuhl D. Noninvasive quantification of regional myocardial blood flow in the human heart using N-13 ammonia and dynamic PET imaging. J Am Coll Cardiol 1990;15:1032–42.

  4. 4.

    Araujo L, Lammertsma A, Rhodes C, et al. Non-invasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. Circulation 1991;83:875–85.

  5. 5.

    Cobb F, Bache R, Greenfield J. Regional myocardial blood flow in awake dogs. J Clin Invest 1974;53:1618–25.

  6. 6.

    Domenech R, Hoffman J, Noble M, Saunders K, Henson J, Subijanto S. Total and regional coronary blood flow measured by microspheres in conscious and anesthetized dogs. Circ Res 1969;25:585–91.

  7. 7.

    LeGrand V, Hodgson J, Bates E, et al. Abnormal coronary flow reserve and abnormal radionuclide exercise test results in patients with normal coronary angiography. J Am Coll Cardiol 1985;6:1245–53.

  8. 8.

    Eisner R, Tamas M, Cloninger K, et al. Normal SPECT thallium-201 bull’s eye display: gender differences. J Nucl Med 1988;29:1901–9.

  9. 9.

    Schelbert H, Wisenberg G, Phelps M, et al. Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilation, VI: detection of coronary artery disease in man with intravenous N-13 ammonia and positron computed tomography. Am J Cardiol 1982;49:1197–207.

  10. 10.

    Tamaki N, Yonekura Y, Senda M, et al. Myocardial positron computed tomography with13N-ammonia at rest and during exercise. Eur J Nucl Med 1985;11:246–51.

  11. 11.

    Yonekura Y, Tamaki N, Senda M, et al. Detection of coronary artery disease with13N-ammonia and high-resolution positron-emission computed tomography. Am Heart J 1987;113:645–54.

  12. 12.

    Tamaki N, Yonekura Y, Senda M, et al. Value and limitation of stress thallium-201 single photon emission computed tomography: comparison with nitrogen-13 ammonia positron tomography. J Nucl Med 1988;29:1181–8.

  13. 13.

    Demer L, Gould K, Goldstein R, et al. Assessment of coronary artery disease severity by positron emission tomography: comparison with quantitative arteriography in 193 patients. Circulation 1989;79:825–35.

  14. 14.

    Go RT, Marwick TH, MacIntyre WJ, et al. A prospective comparison of rubidium-82 PET and thallium-201 SPECT myocardial perfusion imaging utilizing a single dipyridamole stress in the diagnosis of coronary artery disease. J Nucl Med 1990;31:1899–905.

  15. 15.

    Stewart R, Schwaiger M, Molina E, et al. Comparison of rubidium-82 positron emission tomography and thallium-201 SPECT imaging for detection of coronary artery disease. Am J Cardiol 1991;67:1303–10.

  16. 16.

    Berry J, Baker J, Pieper K, Hanson M, Hoffman J, Coleman R. The effect of metabolic milieu on cardiac PET imaging using fluorine-18-deoxyglucose and nitrogen-13-ammonia in normal volunteers. J Nucl Med 1991;32:1518–25.

  17. 17.

    Baudhuin T, Melin T, Marwick T, et al. Regional uptake and blood flow variations with N-13 ammonia in normal subjects do not correlate with flow or metabolic measurements by other methods [Abstract]. J Nucl Med 1992;33:837.

  18. 18.

    Beanlands R, Muzik O, Mintun M, et al. The kinetics of copper-62-PTSM in the normal human heart. J Nucl Med 1992;33:684–90.

  19. 19.

    Schelbert H, Phelps M, Huang S-C, et al. N-13 ammonia as an indicator of myocardial blood flow. Circulation 1981;63:1259–71.

  20. 20.

    Gelbard A, Clarke L, McDonald J, et al. Enzymatic synthesis and organ distribution studies with13N-labeledl-glutamine andl-glutamic acid. Radiology 1975;116:127–32.

  21. 21.

    Green MA. A potential copper radiopharmaceutical for imaging the heart and brain: copper-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone). Nucl Med Biol 1987;15:59–61.

  22. 22.

    Green MA, Klippenstein DL, Tennison JR. Copper(II) bis (thiosemicarbazone) complexes as potential tracers for evaluation of cerebral and myocardial blood flow with PET. J Nucl Med 1988;29:1549–57.

  23. 23.

    Kotzerke J, Hicks R, Wolfe E, et al. Three-dimensional assessment of myocardial oxidative metabolism: a new approach for regional determination of PET-derived carbon-11 acetate kinetis. J Nucl Med 1990;31:1876–93.

  24. 24.

    Selwyn A, Allan R, L’Abbate A, et al. Relation between regional myocardial uptake of rubidium-82 and perfusion: absolute reduction of cation uptake in ischemia. Am J Cardiol 1982;50:112–21.

  25. 25.

    Schwaiger M, Muzik O. Assessment of myocardial perfusion by positron emission tomography. Am J Cardiol 1991;67:35D-43D.

  26. 26.

    Schelbert H, Phelps M, Hoffman E, Huang S, Selin C, Kuhl D. Regional myocardial perfusion assessed with N-13 labeled ammonia and positron emission computerized axial tomography. Am J Cardiol 1979;43:209–18.

  27. 27.

    Hoffman E, Huang S-C, Phelps M. Quantitation in positron emission computed tomography: I, effect of object size. J Comput Assit Tomogr 1979;3:299–308.

  28. 28.

    Marcus M, Kreber R, Erhardt J, Abboud F. Three dimensional geometry of acutely ischemic myocardium. Circulation 1975;52:254–63.

  29. 29.

    Bassingthwaighte JB, King RB, Roger SA. Fractional nature of regional myocardial blood flow heterogeneity. Circ Res 1989;65:578–90.

  30. 30.

    Bassingthwaighte J, Malone M, Moffett T, et al. Validity of microsphere deposition for regional myocardial blood flows. 1987;253:H184–93.

  31. 31.

    King R, Bassingthwaighte J, Hales J, Rowell L. Stability of heterogeneity of myocardial blood flow in normal awake baboons. Circ Res 1985;57:285–95.

  32. 32.

    Bergmann ST, Hack S, Tewson T, Welch MJ, Sobel RE. The dependence of accumulation of13NH3 by myocardium on metabolic factors and its implications for the quantitative assessment or perfusion. Circulation 1980;61:34–43.

  33. 33.

    Krivokapich J, Huang S-C, Phelps M, MacDonald N, Shine K. Dependence of13NH3 by myocardial extraction and retention on flow and metabolism. Am J Physiol 1982;11:H536–42.

  34. 34.

    Krivokapich J, Keen R, Phelps M, Shine K, Barrio J. Effects of anoxia on kinetics [13N]glutamine and13NH3 metabolism in rabbit myocardium. Circ Res 1987;60:505–16.

  35. 35.

    Rosenspire K, Schwaiger M, Mangner T, Hutchins G, Sutorik A, Kuhl D. Metabolic fate of [14N]ammonia in human and canine blood. J Nucl Med 1990;31:163–7.

  36. 36.

    Hicks R, Herman W, Kalff V, et al. Quantitative evaluation of regional substrate metabolism in the human heart by positron emission tomography. J Am Coll Cardiol 1991;18:101–11.

  37. 37.

    Gropler RJ, Siegal BA, Lee KJ, et al. Nonuniformity in myocardial accumulation of F-18 fluorodeoxyglucose in normal fasted humans. J Nucl Med 1990;31:1749–56.

  38. 38.

    Kagaya Y, Kanno Y, Takeyama D, et al. Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats: a quantitative autoradiographic study. Circulation 1990;81:1353–61.

  39. 39.

    Petering DH. The reaction of 3-methoxy-2-oxobutyraldehyde bis (thiosemicarbazonato)copper(II) with thiols. Bioinorg Chem 1972;1:273–388.

  40. 40.

    Winkelmann DA, Bermke Y, Petering DH. Comparative properties of the antineoplastic agent 3-methoxy-2-oxobutyraldehyde bis(thiosemicarbazone)copper(II) and related chelates. Bioinorg Chem 1974;3:261–77.

  41. 41.

    Minkel DT, Saryan LA, Petering DH. Structure-function correlations in the reaction of bis(thiosemicarbazone) copper(II) complexes with Ehrlich ascites tumor cells. Cancer Res 1978;38:124–9.

  42. 42.

    Shelton ME, Green MA, Mathias CJ, Welch MJ, Bergmann SR. Kinetics of copper-PTSM in isolated hearts: a novel tracer for measuring blood flow with positron emission tomography. J Nucl Med 1989;30:1843–7.

  43. 43.

    Shelton M, Green M, Mathias C, Welch M, Bergmann S. Assessment of regional myocardial and renal blood flow with copper-PTSM and positron emission tomography. Circulation 1990;82:990–7.

  44. 44.

    Krivokapich J, Smith G, Huang S, et al.13N ammonia myocardial imaging at rest and with exercise in normal volunteers: quantification of absolute myocardial perfusion with dynamic positron emission tomography. Circulation 1989;80:1328–37.

  45. 45.

    Muzik O, Beanlands R, Hutchins G, Mangner T, Nguyen N, Schwaiger M. Validation of N-13 ammonia tracer kinetic model for quantification of myocardial blood flow using PET. J Nucl Med 1993;34:83–91.

  46. 46.

    Hutchins G, Beanlands R, Muzik O, Schwaiger M. Quantitative vs semi-quantitative PET myocardial blood flow: influence of regional N-13 ammonia kinetics. Circulation 1992;86:I-710.

Download references

Author information

Correspondence to Rob S. B. Beanlands MD or Markus Schwaiger MD.

Additional information

This work was carried out during the tenure of Dr. Schwaiger as an established investigator of the American Heart Association, Dallas, Texas, and was supported in part by National Institutes of Health grant RO1HL41047-01. Dr. Beanlands was a research fellow supported by the Heart and Stroke Foundation of Canada (Ottawa, Canada) until June 30, 1991, and by the Medical Research Council of Canada (Ottawa, Canada) Centennial Fellowship Award from July 1, 1991, to Sept. 30, 1992. Dr. Muzik was supported in part by the Austrian Erwin Schroedinger Foundation Project No. J0473-MED (Vienna, Austria).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Beanlands, R.S.B., Muzik, O., Hutchins, G.D. et al. Heterogeneity of regional nitrogen 13-labeled ammonia tracer distribution in the normal human heart: Comparison with rubidium 82 and copper 62-labeled PTSM. J. Nucl. Cardiol. 1, 225–235 (1994). https://doi.org/10.1007/BF02940336

Download citation

Key Words

  • nitrogen 13-labeled ammonia
  • rubidium 82
  • copper 62-labeled PTSM
  • positron emission tomography
  • myocardium
  • retention